Method and apparatus for cardiac procedures

ABSTRACT

Described herein are methods and apparatus for approximating targeted tissue using locking sutures. The locking sutures can be configured to receive suture ends that are interweaved through portions of the locking sutures. In a pre-deployment configuration, a locking suture can slide along suture tails and can be positioned at a target location within a target region. Once a desired position and/or tension is achieved, the locking suture can be transitioned to a post-deployment configuration where the locking suture constricts around the suture tails to inhibit relative movement between the suture tails and the locking suture.

CROSS-REFERENCE TO RELATED APPLICATION

This application claims the benefit of U.S. Application No. 62/576,364,filed Oct. 24, 2017, which is expressly incorporated by reference hereinin its entirety for all purposes.

BACKGROUND Field

Some embodiments described herein relate to methods and apparatus forjoining two or more sutures together during surgical procedures, such ascardiac valve repairs, and more particularly, methods and apparatus forperforming minimally invasive mitral or tricuspid valve repairs.

Description of Related Art

Various disease processes can impair the proper functioning of one ormore of the valves of the heart. These disease processes includedegenerative processes (e.g., Barlow's Disease, fibroelasticdeficiency), inflammatory processes (e.g., Rheumatic Heart Disease), andinfectious processes (e.g., endocarditis). Additionally, damage to theventricle from prior heart attacks (e.g., myocardial infarctionsecondary to coronary artery disease) or other heart diseases (e.g.,cardiomyopathy) can distort the geometry of the heart causing valves inthe heart to dysfunction. The vast majority of patients undergoing valvesurgery, such as mitral valve surgery, suffer from a degenerativedisease that causes a malfunction in a leaflet of the valve, whichresults in prolapse and regurgitation.

Generally, a heart valve may malfunction in two different ways. Onepossible malfunction, valve stenosis, occurs when a valve does not opencompletely and thereby causes an obstruction of blood flow. Typically,stenosis results from buildup of calcified material on the leaflets ofthe valves causing the leaflets to thicken, thereby impairing theirability to fully open and permit adequate forward blood flow.

Another possible malfunction, valve regurgitation, occurs when theleaflets of the valve do not close completely thereby allowing blood toleak back into the prior chamber when the heart contracts. There arethree mechanisms by which a valve becomes regurgitant or incompetent;they include Carpentier's type I, type II and type III malfunctions. ACarpentier type I malfunction involves the dilation of the annulus suchthat the area of the valve orifice increases. The otherwise normallyfunctioning leaflets do not have enough surface area to cover theenlarged orifice and fail to form a tight seal (e.g., do not coaptproperly) causing regurgitation. Included in a type I mechanismmalfunction are perforations of the valve leaflets, as in endocarditis.A Carpentier's type II malfunction involves prolapse of a segment of oneor both leaflets above the plane of coaptation. This is the mostcommonly treated cause of mitral regurgitation and is often caused bythe stretching or rupturing of chordae tendineae normally connected tothe leaflet. A Carpentier's type III malfunction involves restriction ofthe motion of one or more leaflets such that the leaflets are abnormallyconstrained below the level of the plane of the annulus. Leafletrestriction can be caused by rheumatic heart disease (Ma) or dilation ofthe ventricle (IIIb).

Mitral valve disease is the most common valvular heart disorder, withnearly 4 million Americans estimated to have moderate to severe mitralvalve regurgitation (“MR”), with similar numbers of individuals impactedoutside of the United States. MR results in a volume overload on theleft ventricle which in turn progresses to ventricular dilation,decreased ejection performance, pulmonary hypertension, symptomaticcongestive heart failure, atrial fibrillation, right ventriculardysfunction and death. Successful surgical mitral valve repair restoresmitral valve competence, abolishes the volume overload on the leftventricle, improves symptom status, and prevents adverse leftventricular remodeling. While generally safe and effective, conventionalopen-heart operations are invasive, result in significant disability,and require extended post-procedure recovery. Patients routinely spendfive to seven days in the hospital and often are not able to return tonormal daily activities for a month or more.

Malfunctioning valves may either be repaired or replaced. Repairtypically involves the preservation and correction of the patient's ownvalve. Replacement typically involves replacing the patient'smalfunctioning valve with a biological or mechanical substitute.Typically, replacement is preferred for stenotic damage sustained by theleaflets because the stenosis is irreversible. The mitral valve andtricuspid valve, on the other hand, are more prone to deformation.Deformation of the leaflets, as described above, prevents the valvesfrom closing properly and allows for regurgitation or back flow of bloodfrom the ventricle into the atrium, which results in valvularinsufficiency. Deformations in the structure or shape of the mitralvalve or tricuspid valve are often repairable.

In many instances of mitral valve regurgitation, repair is preferable tovalve replacement. Mitral valve replacement operations have a 2× higherrisk of operative mortality (Risk Standardized Mortality 1.65% vs.2.96%), 2 x higher risk of stroke per year (1.15% vs. 2.2%) and a 10 xhigher risk of infection per year (0.1% vs. 1.0%). Patients who receivea quality mitral valve repair operation do not require anticoagulationand rarely require reoperation. This is in stark contrast to mechanicalvalve replacement which mandates lifelong anticoagulation andbioprosthetic valve replacement with the eventual certainty ofprosthetic valve dysfunction and reoperation. Compared to mitral valvereplacement, mitral valve repair results in improved left ventricularfunction and has superior long-term survival. Therefore, an improperlyfunctioning mitral valve or tricuspid valve is ideally repaired, ratherthan replaced. Because of the complex and technical demands of thecurrent repair procedures, however, the mitral valve is still replacedin approximately one third of all mitral valve operations performed inthe United States.

Studies suggest that Carpentier type II malfunction, often referred toas “Degenerative,” “Primary” or “Organic” MR, accounts for as much as60% of MR. Resectional mitral valve repair techniques, initiallydescribed by Dr. Carpentier, involve cutting out (resecting) a sectionof the prolapsed leaflet tissue, stitching the remaining tissue togetherand implanting an annuloplasty ring around the annulus. Removing aportion of one or both of the mitral valve leaflets during such aresectional repair decreases the available leaflet tissue to seal themitral orifice. To accommodate the decrease caused by the resectionalrepair, in many instances, an annuloplasty ring must be implanted todecrease the size of the mitral orifice.

Implanting an annuloplasty ring introduces various risks. For example,implanting an annuloplasty ring can increase pressure gradients acrossthe valve. Further, an annuloplasty ring can lead to infection and/orannuloplasty ring dehiscence—a well-documented failure mode of valverepair surgery. Implanting an annuloplasty ring can further impact thedynamic nature of the mitral valve annulus throughout the cardiac cycle.In a healthy person, for example, the mitral valve annulus relaxesduring diastole and contracts with the rest of the left ventricle duringsystole, causing the annulus to expand and contract as the heart beats.Implanting an annuloplasty ring can interfere with such normalfunctioning of the heart. To combat such interference, flexibleannuloplasty rings and partial bands have been developed to minimize theimpact a rigid or complete annuloplasty ring can have on the dynamicmovement of the mitral annulus. To avoid the aforementionedcomplications and risks, an effective mitral valve repair procedure thateliminated the need for an annuloplasty ring is desirable, particularlya repair that can be performed minimally-invasively and off-pump inwhich implanting an annuloplasty ring would be present technicalchallenges.

More recently many surgeons have moved to a “non-resectional” repairtechnique where artificial chordae tendineae (“cords”) made of expandedpolytetrafluoroethylene (“ePTFE”) suture, or another suitable material,are placed in the prolapsed leaflet and secured to the heart in the leftventricle, normally to the papillary muscle. Because the native leaflettissue is maintained in non-resectional repairs, they often result in alarger surface of coaptation between the posterior and anterior mitralvalve leaflets, but properly sizing the cords on a flaccid heart can bevery challenging, especially for the low volume mitral valve surgeon.Implanting an annuloplasty ring with such non-resectional repairs on astopped heart is currently the standard of care. Implanting anannuloplasty ring in a beating heart repair is technically challengingand rarely done in practice due in large part to the costs associatedwith two separate procedures (e.g., cordal repair and annuloplasty). Adevice that can quickly and easily perform a beating-heart cordal repairwhile also addressing the mitral annulus would be a major advancement.

Carpentier type I malfunction, sometimes referred to as “Secondary” or“Functional” MR, is associated with heart failure and affects between1.6 and 2.8 million people in the United States alone. Studies haveshown that mortality doubles in patients with untreated mitral valveregurgitation after myocardial infarction. Unfortunately, there is nogold standard surgical treatment paradigm for functional MR and mostfunctional MR patients are not referred for surgical intervention due tothe significant morbidity, risk of complications and prolongeddisability associated with cardiac surgery. Surgeons use a variety ofapproaches ranging from valve replacement to insertion of an undersizedmitral valve annuloplasty ring for patients suffering from functional MRand the long-term efficacy is still unclear. In a randomized study ofon-pump, open-heart mitral valve repair versus mitral valve replacementfor functional MR, mitral valve replacement had a similar mortality rateand resulted in significantly less recurrent MR after one year and twoyears. According to some, a subsequent sub-analysis of subjects in therepair group suggests that the people who received a “good repair” didbetter than the replacement group but that when the repair arm wascompared to mitral valve replacement, the “bad repairs” caused thereplacement arm to perform better. Either way, there is a need forbetter treatment options for functional MR. Less invasive,beating-heart, transcatheter repair and replacement technologies are ofparticular interest because they do not require cardiopulmonary bypass,cardioplegia, aortic cross-clamping or median sternotomy.

Dr. Alfieri has demonstrated the benefit of securing the midpoint ofboth leaflets together creating a double orifice valve in patients withMR known as an “Edge-to-Edge” repair or an Alfieri procedure. Theability to combine a neochordal repair with an edge-to-edge repair indegenerative MR patients with a dilated annulus and who do not receivean annuloplasty ring because the repair is done in a minimally-invasive,off-pump procedure, has particular promise. Further, performing afacilitated edge-to-edge repair in which sutures placed on both theposterior and anterior leaflets are secured together and then pulledtoward the base of the heart has the potential to improve the overallrepair. Performing a facilitated edge-to-edge procedure in aminimally-invasive beating heart procedure is a further advancement.Further, in addition to or instead of creating the edge-to-edgerelationship, to promote a larger surface of coaptation between theanterior and posterior leaflets, and thereby to promote proper valvefunction and limit or prevent undesirable regurgitation, suturesextending from the leaflets can be secured together to pull or tootherwise move the posterior annulus towards the anterior leaflet and/orthe anterior annulus towards to posterior leaflet. This reduces thedistance between the anterior annulus and the posterior annulus (or theseptal-lateral distance) (e.g., by about 10%-30%). Approximating theanterior annulus and the posterior annulus in this manner can decreasethe valve orifice, and thereby decrease, limit, or otherwise preventundesirable regurgitation.

Regardless of whether a replacement or repair procedure is beingperformed, conventional approaches for replacing or repairing cardiacvalves are typically invasive open-heart surgical procedures, such assternotomy or thoracotomy, which require opening up of the thoraciccavity so as to gain access to the heart. Once the chest has beenopened, the heart is bypassed and stopped. Cardiopulmonary bypass istypically established by inserting cannulae into the superior andinferior vena cavae (for venous drainage) and the ascending aorta (forarterial perfusion) and connecting the cannulae to a heart-lung machine,which functions to oxygenate the venous blood and pump it into thearterial circulation, thereby bypassing the heart. Once cardiopulmonarybypass has been achieved, cardiac standstill is established by clampingthe aorta and delivering a “cardioplegia” solution into the aortic rootand then into the coronary circulation, which stops the heart frombeating. Once cardiac standstill has been achieved, the surgicalprocedure may be performed. These procedures, however, adversely affectalmost all of the organ systems of the body and may lead tocomplications, such as strokes, myocardial “stunning” or damage,respiratory failure, kidney failure, bleeding, generalized inflammation,and death. The risk of these complications is directly related to theamount of time the heart is stopped (“cross-clamp time”) and the amountof time the subject is on the heart-lung machine (“pump time”).

Thus, there is a significant need to perform mitral valve repairs usingless invasive procedures while the heart is still beating. Accordingly,there is a continuing need for new procedures and devices for performingcardiac valve repairs, such as mitral valve repair, which are lessinvasive, do not require cardiac arrest, and are less labor-intensiveand technically challenging.

SUMMARY

Apparatus and methods for repairing a tissue by remotely securing two ormore sutures together are described herein. In some embodiments,apparatus and methods for performing a non-invasive procedure to repaira cardiac valve are described herein. In some embodiments, apparatus andmethods are described herein for repairing a mitral valve using anedge-to-edge procedure (also referred to as an Alfieri procedure) usinga locking suture to secure or join portions of the mitral valveleaflets.

In a first aspect, the present disclosure provides a method for usinglocking sutures to approximate anchor implants attached to targetedtissue. The method includes attaching two or more cords to targetedtissue, individual cords including a distal anchor implant and a sutureextending proximally from the distal anchor implant. The method alsoincludes intertwining proximal end portions of the two or more sutureswith a locking suture, the locking suture including a knot portion and atether portion extending from the knot portion and configured to bemanipulated to transition the knot portion from a delivery configurationto a deployed configuration. The method also includes positioning theknot portion of the locking suture along the two or more sutures toapproximate portions of the targeted tissue. The method also includestransitioning the knot portion from the delivery configuration to thedeployed configuration to lock the locking suture. The method alsoincludes receiving feedback from a visualization system, the feedbackincluding an approximation of the targeted tissue.

In some embodiments of the first aspect, transitioning the knot portionto the deployed configuration does not increase proximal forces on thetargeted tissue. In some embodiments of the first aspect, the targetedtissue includes a leaflet of a mitral valve. In some embodiments of thefirst aspect, positioning the locking suture along the sutures of thetwo or more sutures results in a point of intersection that approachesthe targeted tissue to change a force vector on the two or more cordsattached to the targeted tissue.

In some embodiments of the first aspect, the targeted tissue is within atargeted region and positioning the knot portion is done utilizing alocking suture device that is operated outside of the targeted region.In further embodiments of the first aspect, the targeted region is theheart. In further embodiments of the first aspect, the method furtherincludes anchoring the proximal end portions of the two or more sutures.In further embodiments of the first aspect, anchoring the proximal endportions includes securing the proximal end portions to an external wallof the heart.

In some embodiments of the first aspect, the method further includessecuring the knot portion to a distal end of a locking suture deliverydevice. In further embodiments of the first aspect, transitioning theknot portion to the deployed configuration includes manipulating anelement of the locking suture delivery device to which the lockingsuture is secured. In some embodiments of the first aspect, the methodfurther includes applying sequential proximal forces to the proximal endportions using the locking suture delivery device.

In a second aspect, the present disclosure provides a locking suturedelivery and deployment device. The device includes a body having a tipportion at a distal end, the tip portion being configured to beatraumatic to targeted tissue. The device also includes a holdingcomponent coupled to the body, the holding component having one or morefeatures to secure a pre-formed knot of a locking suture at the distalend, the locking suture including a tether portion with two proximalends. The device also includes a release component in communication withthe holding component, the release component configured to release thepre-formed knot after it has been transitioned from a deliveryconfiguration to a deployed configuration. The device also includes atensioning component coupled to the body, the tensioning componentconfigured to apply proximal forces to individual proximal ends of thetether portion at different times with targeted tension.

In some embodiments of the second aspect, the tensioning component isconfigured to transition the pre-formed knot from the deliveryconfiguration to the deployed configuration without increasing tensionon the targeted tissue. In some embodiments of the second aspect, thetensioning component includes a rack and pinion configuration. In someembodiments of the second aspect, the release component includes apusher member to push the pre-formed knot from the holding component.

In some embodiments of the second aspect, the tensioning component isconfigured to apply a first force to a first proximal end portion of thetether portion and to apply a second force to a second proximal end ofthe tether portion. In further embodiments of the second aspect, thetensioning component is configured to apply the first force and thesecond force sequentially without human intervention between applicationof the first force and the second force. In further embodiments of thesecond aspect, the first force and the second force are different fromone another.

In some embodiments of the second aspect, the tensioning component isconfigured to automatically stop increasing tension at a targetedtension. In some embodiments of the second aspect, the tensioningcomponent includes a feedback mechanism to indicate when a targetedtension is achieved.

For purposes of summarizing the disclosure, certain aspects, advantagesand novel features have been described herein. It is to be understoodthat not necessarily all such advantages may be achieved in accordancewith any particular embodiment. Thus, the disclosed embodiments may becarried out in a manner that achieves or optimizes one advantage orgroup of advantages as taught herein without necessarily achieving otheradvantages as may be taught or suggested herein.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 illustrates schematically a locking suture deployed within atarget region for approximating tissues therein, according to anembodiment.

FIGS. 2A, 2B, 2C, and 2D illustrate schematically a method and devicefor approximating tissues using a LS delivery device, according to anembodiment.

FIGS. 3A, 3B, 3C, and 3D illustrate schematically and conceptually amethod of deploying the locking suture of FIGS. 2A-2D.

FIG. 4 illustrates a cut-away anterior view of a heart, showing theinternal chambers, valves and adjacent structures.

FIG. 5A illustrates a top perspective view of a healthy mitral valvewith the mitral leaflets closed.

FIG. 5B illustrates a top perspective view of a dysfunctional mitralvalve with a visible gap between the mitral leaflets.

FIG. 5C illustrates a cross-sectional view of a heart illustrating amitral valve prolapsed into the left atrium.

FIG. 5D illustrates an enlarged view of the prolapsed mitral valve ofFIG. 5C.

FIG. 6 illustrates a cross-sectional view of a heart showing the leftatrium, right atrium, left ventricle, right ventricle and the apexregion.

FIG. 7 illustrates a block diagram of an example LS delivery devicehaving a knot holder and atraumatic tip with a tensioner and releasemechanism.

FIG. 8 illustrates a flow chart of an example method for securing alocking suture to approximate distal anchors attached to tissue

FIG. 9 is a schematic illustration of a mitral valve with leaflets thatare separated by a gap.

FIGS. 10A, 10B, 10C, and 10D illustrate a method using a LS deliverydevice to deliver and deploy a locking suture, according to anembodiment.

FIGS. 11A, 11B, 11C, 11D, 11E, 11F, and 11G illustrate a method offorming a knot portion of a locking suture about a knot holder,according to an embodiment.

FIGS. 12A, 12B, 12C, 12D, and 12E illustrate an alternate approach forforming the locking suture knot portion of FIGS. 11A-11G.

FIG. 13 illustrates in right side view a LS delivery device, accordingto an embodiment.

FIG. 14 illustrates in left side view the LS delivery device of FIG. 13.

FIGS. 15A and 15B illustrate detailed top views of the knot pusher ofthe LS delivery device of FIG. 13 with a knot holder in an extendedposition and a retracted position, respectively.

FIG. 15C illustrates a detailed side view of the knot pusher of the LSdelivery device of FIG. 13 with a knot holder in an extended position.

FIG. 15D illustrates a detailed front view of the knot pusher of the LSdelivery device of FIG. 13 with a knot holder in disposed within thelumen of the knot pusher.

FIG. 15E illustrates a detailed perspective view of the knot pusher, theknot end effector, and the knot holder extending distally therefrom.

FIG. 15F illustrates a detailed front view version of FIG. 15E.

FIG. 15G illustrates a detailed bottom perspective view version of FIG.15E.

FIG. 15H illustrates a detailed top view version of FIG. 15E.

FIG. 15I illustrates a detailed front perspective view version of FIG.15E.

FIGS. 16A, 16B, 16C, 16D, 16E, 16F, 16G, 16H, 16I, 16J, 16K, 16L, 16M,16N, 160, 16P, 16Q, 16R, 16S, 16T, 16U, 16V, 16W, 16X, 16Y, 16Z, 16AA,16AB, 16AC, 16AD, 16AE, 16AF, 16AG, 16AH, 16AI, 16AJ, and 16AKillustrate a method of preparing the locking suture of the LS deliverydevice of FIG. 13 for delivery and deployment.

FIG. 16AL illustrates the locking suture of FIGS. 16A-16AK deployed andsecured to sutures extending from implants.

FIGS. 17A, 17B, 17C, 17D, 17E, 17F, 17G, 17H, 17I, 17J, 17K, 17L, 17M,17N, 170, 17P, 17Q, 17R, 17S, 17T, 17U, 17V, and 17W illustrate analternate method of forming the locking suture described with referenceto FIGS. 16A-16AK.

FIGS. 18A, 18B, 18C, 18D, 18E, 18F, 18G, 18H, 18I, 18J, 18K, 18L, and18M illustrate another example LS delivery device with a tensioningmechanism that includes a rack and pinion configuration.

FIG. 19 illustrates a flowchart of an example method of delivering anddeploying a locking suture to approximate mitral valve leaflets,according to an embodiment.

FIG. 20 illustrates a locking suture disposed about a knot holder in anelongated configuration, according to an embodiment.

FIG. 21 illustrates the locking suture of FIG. 20 in a deployed knotconfiguration.

FIGS. 22A, 22B, and 22C illustrate an edge-to-edge procedure for amitral valve using the locking sutures and delivery devices describedherein.

DETAILED DESCRIPTION OF SOME EMBODIMENTS

The headings provided herein, if any, are for convenience only and donot necessarily affect the scope or meaning of the claimed invention.

Overview

During conventional, on-pump cardiac operations, the heart is stoppedand the doctor has vision of and direct access to the internalstructures of the heart. In conventional operations, doctors perform awide range of surgical procedures on a defective valve. In degenerativemitral valve repair procedures, techniques include, for example andwithout limitation, various forms of resectional repair, chordalimplantation, and edge-to-edge repairs. Clefts or perforations in aleaflet can be closed and occasionally the commissures of the valvesutured to minimize or eliminate MR. Although devices have beendeveloped to replicate conventional mitral valve procedures on a beatingheart (see, e.g., International Patent Application No.PCT/US2012/043761, published as WO 2013/003228 A1, and referred toherein as “the '761 PCT Application”) there is a need to expand the“toolbox” available to doctors during these minimally invasiveprocedures.

The ability to remotely (e.g., from outside the heart during a cardiacvalve repair) and adjustably secure two or more otherwise separatestrands of suture together within a body has wide ranging applications.One application, for example, is in minimally-invasive, beating-heart,cardiac procedures. The ability to remotely secure two or more suturestrands together while the heart is beating should dramatically expandthe utility of the devices that have been used in cardiac operations todate.

In some embodiments, a method for repairing tissue includes inserting adelivery device, such as a delivery device described in the '761 PCTApplication and/or in International Patent Application No.PCT/US2016/055170 (published as WO 2017/059426A1 and referred to hereinas “the '170 PCT Application”), the entire disclosure of each of whichis incorporated herein by reference, into a body and extending a distalend of the delivery device to a proximal side of the tissue. Advancementof the delivery device may be performed in conjunction with sonographyor direct visualization (e.g., direct transblood visualization), and/orany other suitable remote visualization technique. With respect tocardiac procedures, for example, the delivery device may be advanced inconjunction with transesophageal (TEE) guidance or intracardiacechocardiography (ICE) guidance to facilitate and to direct the movementand proper positioning of the device for contacting the appropriatetarget cardiac region and/or target cardiac tissue (e.g., a valveleaflet, a valve annulus, or any other suitable cardiac tissue). Typicalprocedures for use of echo guidance are set forth in Suematsu, Y., J.Thorac. Cardiovasc. Surg. 2005; 130:1348-56 (“Suematsu”), the entiredisclosure of which is incorporated herein by reference.

A piercing portion of the delivery device can be used to form an openingin the tissue, through which the distal end of the delivery device canbe inserted. The delivery device can be used to form or deliver animplant (e.g., a distal anchor) to the distal side of the tissue. Thedelivery device can be used in this manner to deliver two or moreimplants to the distal side of the tissue. The implants can be deliveredto a single tissue (e.g., a posterior mitral valve leaflet), or one ormore implants can be delivered to a first tissue (e.g., a posteriormitral valve leaflet), and one or more other implants can be deliveredto a second tissue (e.g., an anterior mitral valve leaflet, a mitralvalve annulus, or any other suitable tissue) separate from the firsttissue. The delivery device can then be withdrawn, and suture portionsextending from the implants can extend to a location (e.g., an outsidesurface of the heart or other suitable organ) remote from the tissue(s).The remote suture portions can then be coupled to a locking suturedelivery and deployment device (also referred to as a locking suturedevice or locking suture delivery device) that can be operated fromoutside the target region to deliver and to deploy a locking suturewithin the targeted region about the suture portions extending from thetissue(s). Advantageously, using the methods and apparatus disclosedherein, introducing additional foreign objects, such as, for example, asecuring device, to an area within the target region (e.g., the heart)within which the tissues are located, can be avoided. For example, in anon-invasive cardiac procedure to repair cardiac tissue(s) within theheart, the locking suture device can remain outside the heart and can beused to selectively and remotely secure the suture portions extendingfrom the implants and to selectively, reversibly, and controllablyapproximate the tissue(s) from which the suture portions extend.

In addition, applications exist that use knotting, joining, securing,and/or approximating multiple sutures together. In connection with anannuloplasty procedure, for example, one or more pairs of sutures can beused to secure the annuloplasty ring around the mitral annulus. Thesuture pairs may be joined using embodiments of the devices and methodsdisclosed herein. As another example, in connection with a procedure(e.g., a mitral valve repair) in which multiple suture tails or freeends extend outside the heart, it may be useful to join those suturesand secure them to an anchor (e.g., a pledget) outside the heart. In yeta further example, it may be useful to join and to tie down multiplesutures in connection with addressing congenital intracardiac defects.As yet another example, knotting, joining, securing, and/orapproximating multiple sutures together may be useful in minimallyinvasive thoracic and/or abdominal surgeries where, for example, thereis restrictive or limited space (e.g., when working through relativelysmall trocar portal(s)). Another example includes using sutures torestrict or cut off blood flow in a damaged blood vessel, such as in thebrain. The disclosed locking sutures, devices, and methods can be usedto secure sutures in a way that restricts blood flow through targetedblood vessels.

Thus, there is a significant need to knot, join, secure, and/orapproximate multiple sutures together in various medical applications inaddition to mitral valve repairs. Accordingly, there is a continuingneed for new procedures and devices which are less invasive, lesslabor-intensive, and less technically challenging. Examples of suchprocedures and devices are disclosed herein.

FIG. 1 illustrates schematically an example of a locking suture 137deployed within a target region TR for approximating tissues T1, T2therein. The locking suture 137 includes a knot portion 137Aconfigurable between a delivery configuration and a deployedconfiguration, and a tether portion 137B extending from the knot portion137A and configured to be manipulated outside the target region TR totransition the knot portion 137A within the target region TR from itsdelivery configuration to its deployed configuration. As shown, with afirst suture portion 132 extending from an implant 131 secured to tissueT1 and a second suture portion 134 extending from an implant 131′secured to tissue T2, the locking suture 137 can be secured within thetarget region TR to both the first suture portion 132 and the secondsuture portion 134, and can be anchored to a location outside the targetregion TR.

As described in greater detail herein, translating or moving the lockingsuture 137 distally and/or proximally along the free ends of the sutures132, 134 can change the distance between the implants 131, 131′ andtherefore the tissues T1, T2. Once a targeted tissue or implantapproximation is achieved, the locking suture 137 can be locked bytransitioning the knot portion 137A from its delivery configuration toits deployed configuration using the tether portion 137B.

The locking suture 137 can be formed of any suitable material. In someinstances, for example, the locking suture can made of one or more ofexpanded polytetrafluoroethylene (“ePTFE”) suture, polybutylate-coatedpolyester suture, or polyester suture (such as, for example, EthibondExcel® Polyester Suture, Johnson & Johnson, New Brunswick, N.J.). Insome instances, the locking suture can be modified to increase itscoefficient of friction to improve its locking capability. The lockingsuture, made from ePTFE for example, can be braided, twisted, or knotted(e.g., with overhand knots). Additionally, or alternatively, in someinstances, the locking suture's thickness and/or surface texture (e.g.,textured surface, coating, etc.) can be configured to increase itscoefficient of friction and/or improve its locking capabilities.

In some implementations, the implants 131, 131′ can be delivered anddisposed on an atrial, distal, or top side of heart valve leaflets(e.g., mitral valve leaflets). The implants 131, 131′ can be formed witha suture material that forms a loop on the atrial, distal, or top sideof the leaflets and extends through the leaflets, with two loose sutureend portions that extend on the ventricular, proximal, or bottom side ofthe leaflets. In some embodiments, implants can be formed separatelyfrom and then attached to the suture end portions. In this manner, theimplants can be attached to the suture material, deployed on the atrialside of the leaflets, and the suture end portions can extend from theimplants and through the leaflets to the ventricular side of theleaflets, and then anchored outside the target region TR (e.g., theheart) as described in further detail herein.

The knot portion 137A of the locking suture 137 when in its deliveryconfiguration (as described in further detail below) can be slidablycoupled to and delivered (e.g., pushed distally) along the sutureportions 132, 134 into and through the target region TR using a deliverydevice that is operated from outside the target region TR (e.g.,controlled remotely and delivered minimally invasively). The knotportion 137A can be in the form of braided, twisted, coiled, looped,and/or knotted lines (e.g., sutures). In a delivery configuration, theknot portion 137A can be loose enough to allow a plurality of sutures toslide therethrough. In a delivery configuration, the knot portion 137Acan be constricted to create a tortuous path for the plurality ofsutures passing through the knot portion. For example, the knot portion137A can be in the form of one or more multi-turn coils distributedabout various regions of the suture portions 132, 134, and the coils canbe changed from an elongated, delivery configuration, in which the knotportion 137A is slidable, translatable, and/or pushable along or aboutthe suture portions 132, 134 while maintaining its integrity (e.g., itscoiled formation), to a deployed configuration by constricting the coilsand/or approximating opposite ends of the coil(s) towards each other tolock or secure the knot portion 137A to the suture portions 132, 134 andinhibit relative motion therebetween.

As described in further detail below, to deploy knot portion 137A (e.g.,to transition the knot portion 137A from its delivery configuration toits deployed configuration), the tether portion 137B can be pulledproximally. This causes the knot portion 137A to constrict on the sutureportions 132, 134 so that they are secured together within the knotportion 137A at a targeted location within the target region TR relativeto the tissues T1, and T2. In addition, the knot portion 137A can besecured in a way that the knot portion 137A does not move distally orproximally along the suture portions 132, 134. With the knot portion137A secured or locked to the suture portions 132, 134 at a targetedlocation within the target region TR, the free ends of the sutureportions 132, 134 and the free ends of the tether portion 137B extend toa location outside the target region TR. In this configuration, thetether portion 137B and the free ends of the suture portions 132, 134can be coupled to and secured outside the target region TR using aproximal anchor 144. For example, the tether portion 137B and the freeends of the suture portions 132, 134 can be secured via the proximalanchor 144 to an external or outer surface of a tissue, such as theheart.

FIGS. 2A, 2B, 2C, and 2D illustrate schematically examples of a methodand a device for approximating tissues T1, T2 (e.g., mitral valveleaflets within a heart) by delivering and deploying a locking suture237 using a locking suture (LS) delivery device 246. Advantageously,with the LS delivery device 246 disposed partially outside the targetregion TR, a user can control or manipulate the LS delivery device 246from outside the target region TR to deliver and to deploy the lockingsuture 237 within the target region TR.

FIG. 2A illustrates a first suture portion 232 extending from a firstimplant 231 secured to a first tissue T1 and a second suture portion 234extending from a second implant 231′ secured to a second tissue T2. Thefirst suture portion 232 and the second suture portion 234 can extend toa location remote from the tissues T1, T2 (e.g., an outer surface of theheart), and can be operably coupled to the LS delivery device 246outside the target region TR. The first and second suture portions 232,234 can be passed through the locking suture 237 that is coupled to anend of the LS delivery device 246. In some embodiments, the first andsecond suture portions 232, 234 can be threaded through portions of thelocking suture. In some embodiments, the first and second sutureportions 232, 234 can pass through a central portion of the lockingsuture 237 (e.g., a lumen formed by one or more coils of the lockingsuture 237). Advantageously, although each suture portion 232, 234 iscoupled to the LS delivery device 246 remote from the tissues T1, T2 andis outside the target region TR, the LS delivery device 246 can deliverand deploy the locking suture 237 within the target region TR toapproximate the tissues T1, T2.

FIG. 2B illustrates inserting a portion of the LS delivery device 246into the target region TR to move the locking suture 237 to a targetedlocation. In some embodiments, actuation of the LS delivery device 246can operate (1) to deliver the locking suture 237 in its deliveryconfiguration, and (2) to transition the locking suture 237 into itsdeployed configuration. In its delivery configuration, the knot portion237A of the locking suture 237 is able to slide or translate along, orotherwise move relative to, the suture portions 232, 234, to a targetedlocation within the target region TR. In its deployed configuration, theknot portion 237A of the locking suture 237 is tightened, compressed(e.g., radially and/or laterally), cinched, or otherwise secured to thesuture portions 232, 234.

More specifically, to deliver the locking suture 237, the LS deliverydevice 246 is used to push, urge, slide, translate or otherwise move theknot portion 237A in its delivery configuration distally along thesuture portions 232, 234 within the target region TR. Movement of theknot portion 237A can be along a translation axis 247 that ispreferably, but not necessarily, oriented between the axes of the sutureportions 232, 234. In some embodiments, the axis 247 may approximatelybisect the angle α defined between the axes of the suture portions 232,234.

As the LS delivery device 246 is used to move the knot portion 237Adistally into the target region TR and towards the tissues T1, T2, thesuture portions 232, 234 define a point of intersection 299 of the axesof the suture portions 232, 234. As the LS delivery device 246 furtherurges the knot portion 237A distally within the target region TR, thepoint of intersection 299 is moved towards the implants 231, 231′ (andthus the tissues T1, T2), the lengths of the suture portions 232, 234between the point of intersection 299 and the respective tissues T1, T2shorten, and the angle α defined between the axes of the suture portions232, 234 increases.

With the knot portion 237A delivered to a targeted, suitable, ordesirable position (e.g., causing a targeted approximation of thetissues T1, T2), the tether portion 237B can be pulled proximally orwithdrawn to deploy the knot portion 237A. Deployment of the knotportion 237A inhibits relative movement between the knot portion 237Aand the suture portions 232, 234 disposed therein. Advantageously,pulling the tether portion 237B does not significantly increase or alterthe tension on the suture portions 232, 234 and, consequently, the forceor tension on the distal anchors 231, 231′ and the tissue T1, T2 doesnot significantly change during deployment of the knot portion 237A.Likewise, while deploying the knot portion 237A, the force or tensionapplied to the tether portion 237B that causes the knot portion 237A todeploy is directed to the knot portion 237A at the distal tip of the LSdelivery device 246 and not to the distal anchors 231, 231′ or thetissues T1, T2. Thus, the suture portions 232, 234, the distal anchors231, 231′, and/or the tissues T1, T2 can be free from any additionaltension or force applied when deploying the knot portion 237A. This maybe due at least in part to the design of the distal end of the LSdelivery device 246. For example, as described herein, the distal tip ofthe LS delivery device 246 can include one or more features that anglethe tether portion 237B at a desired angle so that stress applied to thetether portion 237B causes the knot portion 237A to constrict or tightenwhile not applying significant proximal force that may cause the knotportion 237A to pull proximally on the suture portions 232, 234.

FIG. 2C illustrates the locking suture 237 in its deployedconfiguration, secured to the first and second suture portions 232, 234.After delivery and deployment of the locking suture 237, the LS deliverydevice 246 can be withdrawn proximally (e.g., along the suture portions232, 234 extending proximally from the locking suture 237) and removedfrom the target region TR. Removing the LS delivery device 246 leavesbehind the deployed locking suture 237 secured to the suture portions232, 234 at a targeted location within the target region TR. In someembodiments, the targeted location can be selected or based on atargeted approximation of tissues T1, T2 and/or a targeted amount oftension applied by the suture portions 232, 234 to the tissues T1, T2.In certain embodiments, the free ends of the suture end portions 232,234 and the free ends of the tether portion 237B can extend from thedeployed locking suture 237 within the target region TR to an areaoutside the target region TR. These ends can be secured via a proximalanchor 244 outside the target region TR (e.g., against an outer surfaceof the heart).

As illustrated in FIG. 2D, a force, F, applied to the locking suture 237and/or to the two suture portions 232, 234 (and considering each sutureportion 232, 234 as a pure tension member), results in an axial force,Fs, carried by each suture portion 232, 234 between the knot portion237A and the tissues T1, T2 along the respective axes of the sutureportions 232, 234. Each axial force, Fs, can be decomposed into a firstcomponent, Fa, that is parallel to the axis 247 that bisects the angle αand a second component, Fb, that is perpendicular to the axis 247. Thesecond component, Fb, of the axial force, Fs, in each suture portion232, 234 acts to approximate, or draw together, the tissue T1, T2 towhich the implants 231, 231′ are coupled.

The LS delivery device 246 can be used to slide the knot portion 237Adistally or proximally along the suture portions 232, 234 to change theangle α and the location of the point of intersection 299. For example,pushing the knot portion 237A distally approximates the implants 231,231′. Similarly, pulling the knot portion 237A proximally reduces theamount of approximation of the implants 231, 23P. For example, the LSdelivery device 246 can be withdrawn (e.g., when in its deliveryconfiguration) proximally before the locking suture 237 is deployed towithdraw the knot portion 237A proximally to reduce the approximation ofthe implants 231, 231′. Thus, the degree of approximation can beincreased or decreased until the desired or targeted approximation isachieved. In some implementations, the targeted degree of approximationcan be confirmed under image guidance (e.g., echocardiography). The LSdelivery device 246 can then be actuated to transition the knot portion237A of the locking suture 237 from its delivery configuration to itsdeployed configuration to lock, radially and/or laterally compress(described in more detail herein), and/or otherwise secure the lockingsuture 237 in place relative to the suture portions 232, 234. Thisresults in the degree of approximation of the implants 231, 231′ beingsubstantially secured and maintained after the LS delivery device 246 isremoved. The LS delivery device 246 can then be withdrawn from thetarget region TR and decoupled or withdrawn from the suture portions232, 234 and the tether portion 237B. The suture portions 232, 234 andthe free ends of the locking suture 237 can be secured outside thetarget region TR in a suitable location (e.g., an outer surface of theheart) with, for example, a proximal anchor 244.

As described herein, the knot portion 237A has (1) a deliveryconfiguration in which the locking suture 237 is pushable, slidable ordeliverable along or about the suture portions 232, 234, and (2) adeployed configuration in which the knot portion 237B is further engagedwith, further constricted about, compressed (e.g., radially and/orlaterally), cinched, secured, tightened, or fixed to the suture portions232, 234, such that relative motion between the knot portion 237A and aportion of the suture portions 232, 234 is inhibited and/or prevented.In the delivery configuration, the knot portion 237A is wrapped,intertwined, looped, turned, wound, or otherwise engaged with the sutureportions 232, 234 in a manner that allows the locking suture 237 tomaintain its structural integrity (e.g., its coiled disposition) suchthat it is in a ready-state to be deployed, while allowing sufficientrelative movement between the locking suture 237 and the suture portions232, 234. This allows the knot portion 237A to be moved distally and/orproximally along the suture portions 232, 234.

FIGS. 3A-3D conceptually illustrate a segment of the knot portion 237Aof FIGS. 2A-2D disposed about the suture portions 232, 234 as ittransitions from a delivery configuration to a deployed configuration.For ease of description, transitioning to the deployed configuration ispresented as having a number of sequential stages, however, it is to beunderstood that the stages or portions of the stages may occursimultaneously or in a different order. FIG. 3A illustrates the segmentof the knot portion 237A in the delivery configuration disposed aboutthe suture portions 232, 234. FIG. 3B illustrates the segment of theknot portion 237A in a first stage of the deployed configuration wherethe knot portion 237A experiences radial compression. FIG. 3Cillustrates the segment of the knot portion 237A in a second stage ofthe deployed configuration where the knot portion 237A experienceslateral compression. FIG. 3D illustrates the segment of the knot portion237A in a different second stage of the deployed configuration that islimited to axial compression of the knot portion 237A.

With reference to FIG. 3A where the knot portion 237A is in the deliveryconfiguration, the locking functionality of the knot portion 237A can bedecomposed into multiple locking portions that individually provideforces against the suture portions 232, 234 disposed therebetween. Forexample, a first portion 237A-1 provides a first force component Fa1, asecond portion 237A-2 provides a second force component Fb1, and a thirdportion 237A-3 provides a third force component Fc1. Note that the threeportions 237A-1, 237A-2, 237A-3 and their respective associated forcecomponents Fa1, Fb1, Fc1 represent example locations from which forcesare applied by the knot portion 237A of the locking suture 237. Itshould be understood, however, that in practice the knot portion 237Acan provide circumferentially continuous compressive, constrictive, orlocking force components or vectors about the suture portions 232, 234,as more clearly evident in embodiments described herein.

The arrow A represents a direction of allowable movement or translationof the suture portions 232, 234 relative to the knot portion 237A whenin the delivery configuration. That is, in the delivery configurationthe locking suture 237 is sufficiently loosely wound, wrapped, and/orcoiled around the suture portions 232, 234 in an elongated manner thatthe locking suture 237 can be moved along the suture portions 232, 234.This can be done, for example, to deliver the locking suture 237 intothe target region TR and towards the tissues T1, T2 (which is describedin greater detail herein with reference to FIGS. 2A and 2B). With theknot portion 237A delivered to a targeted location, the locking suture237 can be deployed or transitioned into a tightened, bulky, bunched, orlooped knot configuration. This can be accomplished, for example, byapproximating opposite ends of the winds or coils of the locking suture237 towards each other.

During deployment, the coils, wraps, loops, turns, or portions of theknot portion 237A disposed about the suture portions 232, 234 aretightened, shortened, and/or constricted, resulting in a restrained orconfined tortuous path for the suture portions 232, 234, as illustratedconceptually in FIGS. 3B, 3C, and 3D. With reference to FIG. 3B, themagnitude of the force components Fa2, Fb2, Fc2 applied by therespective portions 237A-1, 237A-2, 237A-3 of the knot portion 237A inthe first stage of its deployed configuration is greater than amagnitude of the force components Fa1, Fb1, Fc1 in the deliveryconfiguration shown in FIG. 3A, resulting in the respective lockingsuture portions 237A-1, 237A-2, 237A-3 moving towards the sutureportions 232, 234, e.g., towards axis B. This biases the suture portions232, 234 into a tortuous configuration. Said another way, during thefirst stage of deployment, the knot portion 237A is radially compressedabout the suture portions 232, 234 by opposing forces, e.g., forces Fa2and Fc2 oppose force Fb2, thereby increasing the friction between theknot portion 237A and the suture portions 232, 234 and restrictingrelative movement therebetween. To deploy this first stage and radiallycompress the knot portion 237A about the suture portions 232, 234, onestrand or free end of the tether portion 237B can be pulled or withdrawnproximally. Such radial compression is illustrated by the opposingmovements of the first and third locking portions 237A-1 237A-3 relativeto the second locking portion 237A-2. After the first stage, a secondstage of deployment can include pulling on the other strand or free endof the tether portion 237B to laterally or angularly deflect the firstportion 237A-1 (e.g., along arrow C, about the B axis, and/or about thesecond portion 237A-2) to create a bulky or looped configuration tofurther secure and inhibit relative movement of the suture portions 232,234, as illustrated in FIG. 3C. In some embodiments, examples of whichare illustrated in FIG. 3D, the second stage of deployment can involveonly axial compression of knot portion 237A, e.g., reducing the axialspacing of first, second, and third locking portions 237A-1, 237A-2, and237A-3 along axis B. With the knot portion 237A sufficiently secured tothe suture portions 232, 234 in this manner, the free ends of the sutureportions 232, 234 and the tether portion 237B can be dealt with in anysuitable manner. For example, in some instances, the free ends of thesuture portions 232, 234 and the tether portion 237B can be securedoutside the target region (e.g., to an external surface of the heart).

Although the above embodiment with respect to the LS delivery device 246describes a method using examples dealing with a cardiac procedure, themethods and devices described herein are readily adaptable for varioustypes of tissue repair procedures. For ease of explanation, embodimentsdescribed herein are described with respect to repairing a cardiacmitral valve. It should be understood, however, that the devices andmethods described herein can be used to repair other cardiac valves,such as a tricuspid, aortic, or pulmonic valve, or non-valvular cardiactissue, such as heart walls and/or septa, or non-cardiac tissues, suchas in orthopedic applications where two or more tissues are to beapproximated. Similarly, the devices and methods described herein can beused in applications in which two or more sutures or the like are to beapproximated, knotted, joined, and/or secured together. In connectionwith cardiac surgery, for example, in a procedure in which artificialcords are secured to a native valve leaflet and/or annulus, the freeends of the cords may extend outside the heart. With the free ends ofthe cords disposed outside the heart, the devices and methods describedherein can be used to secure the cords together outside the heart, andoptionally, for example, to a pledget or similar anchor.

In some embodiments, for example, apparatus and methods are describedherein for remotely securing two or more sutures together within anon-invasive procedure to repair a cardiac valve. In some embodiments,apparatus and methods are described herein for performing a non-invasiveprocedure for repairing a mitral valve using an edge-to-edge stitch(also referred to as an Alfieri procedure) to secure two mitral valveleaflets together.

As illustrated in FIG. 4, the human heart 10 has four chambers, whichinclude two upper chambers denoted as atria 12, 16 and two lowerchambers denoted as ventricles 14, 18. A septum 20 (see, e.g., FIG. 6)divides the heart 10 and separates the left atrium 12 and left ventricle14 from the right atrium 16 and right ventricle 18. The heart furthercontains four valves 22, 23, 26, and 27. The valves function to maintainthe pressure and unidirectional flow of blood through the body and toprevent blood from leaking back into a chamber from which it has beenpumped.

Two valves separate the atria 12, 16 from the ventricles 14, 18, denotedas atrioventricular valves. The mitral valve 22, also known as the leftatrioventricular valve, controls the passage of oxygenated blood fromthe left atrium 12 to the left ventricle 14. A second valve, the aorticvalve 23, separates the left ventricle 14 from the aortic artery (aorta)29, which delivers oxygenated blood via the circulation to the entirebody. The aortic valve 23 and mitral valve 22 are part of the “left”heart, which controls the flow of oxygen-rich blood from the lungs tothe body. The right atrioventricular valve, the tricuspid valve 24,controls passage of deoxygenated blood into the right ventricle 18. Afourth valve, the pulmonary valve 27, separates the right ventricle 18from the main pulmonary artery 25. The right ventricle 18 pumpsdeoxygenated blood through the pulmonary artery 25 to the lungs whereinthe blood is oxygenated and then delivered to the left atrium 12 via thepulmonary vein. Accordingly, the tricuspid valve 24 and pulmonic valve27 are part of the right heart, which control the flow ofoxygen-depleted blood from the body to the lungs.

Both the left and right ventricles 14, 18 constitute pumping chambers.The aortic valve 23 and pulmonic valve 27 lie between a pumping chamber(ventricle) and a major artery and control the flow of blood out of theventricles and into the circulation. The aortic valve 23 and pulmonicvalve 27 have three cusps, or leaflets, that open and close and therebyfunction to prevent blood from leaking back into the ventricles afterbeing ejected into the lungs or aorta 29 for circulation.

Both the left and right atria 12, 16 are receiving chambers. The mitralvalve 22 and tricuspid valve 24, therefore, lie between a receivingchamber (atrium) and a ventricle so as to control the flow of blood fromthe atria to the ventricles and prevent blood from leaking back into theatrium during ejection from the ventricle. Both the mitral valve 22 andtricuspid valve 24 include two or more cusps, or leaflets (not shown inFIG. 4), that are encircled by a variably dense fibrous ring of tissuesknown as the annulus (not shown in FIG. 4). The valves are anchored tothe walls of the ventricles by chordae tendineae (chordae) 17. Thechordae tendineae 17 are cord-like tendons that connect the papillarymuscles 19 to the leaflets (not shown in FIG. 4) of the mitral valve 22and tricuspid valve 24 of the heart 10. The papillary muscles 19 arelocated at the base of the chordae tendineae 17 and are within the wallsof the ventricles. The papillary muscles 19 do not open or close thevalves of the heart, which close passively in response to pressuregradients; rather, the papillary muscles 19 brace the valves against thehigh pressure needed to circulate the blood throughout the body.Together, the papillary muscles 19 and the chordae tendineae 17 areknown as the sub-valvular apparatus. The function of the sub-valvularapparatus is to keep the valve leaflets from prolapsing into the atriawhen they close.

The mitral valve 22 is illustrated in FIG. 5A. The mitral valve 22includes two leaflets, the anterior leaflet 52 and the posterior leaflet54, and a diaphanous incomplete ring around the valve, called theannulus 53. The mitral valve 22 has two papillary muscles 19, theanteromedial and the posterolateral papillary muscles (see, e.g., FIG.4), which attach the leaflets 52, 54 to the walls of the left ventricle14 via the chordae tendineae 17 (see, e.g., FIG. 4).

FIG. 5B illustrates a prolapsed mitral valve 22. As can be seen withreference to FIG. 5B-5D, prolapse occurs when a prolapsed segment of aleaflet 52, 54 of the mitral valve 22 is displaced above the plane ofthe mitral annulus into the left atrium 12 (see FIGS. 5C and 5D)preventing the leaflets from properly sealing together to form thenatural plane or line of coaptation between the valve leaflets duringsystole. Because one or more of the leaflets 52, 54 malfunctions, themitral valve 22 does not close properly, and, therefore, the leaflets52, 54 fail to coapt. This failure to coapt causes a gap 55 between theleaflets 52, 54 that allows blood to flow back into the left atrium,during systole, while it is being ejected by the left ventricle. As setforth above, there are several different ways a leaflet may malfunction,which can thereby lead to regurgitation.

Mitral valve regurgitation increases the workload on the heart and maylead to very serious conditions if left untreated, such as decreasedventricular function, pulmonary hypertension, congestive heart failure,permanent heart damage, cardiac arrest, and ultimately death. Since theleft heart is primarily responsible for circulating the flow of bloodthroughout the body, malfunction of the mitral valve 22 is particularlyproblematic and often life threatening.

As described in detail in the '761 PCT Application and the '170 PCTApplication, methods and devices are provided for performingnon-invasive procedures to repair a cardiac valve, such as a mitralvalve. Such procedures include procedures to repair regurgitation thatoccurs when the leaflets of the mitral valve do not coapt at peakcontraction pressures, resulting in an undesired back flow of blood fromthe ventricle into the atrium. As described in the '761 PCT Applicationand the '170 PCT Application, after the malfunctioning cardiac valve hasbeen assessed and the source of the malfunction verified, a correctiveprocedure can be performed. Various procedures can be performed inaccordance with the methods described therein to effectuate a cardiacvalve repair, which will depend on the specific abnormality and thetissues involved.

After preparing and placing the subject under anesthesia, atransesophageal echocardiogram (TEE) (2D or 3D), a transthoracicechocardiogram (TTE), intracardiac echo (ICE), or cardio-optic directvisualization (e.g., via infrared vision from the tip of a 7.5 Fcatheter) may be performed to assess the heart and its valves.

After a minimally invasive approach is determined to be advisable, oneor more incisions are made proximate to the thoracic cavity to provide asurgical field of access. The total number and length of the incisionsto be made depend on the number and types of the instruments to be usedas well as the procedure(s) to be performed. The incision(s) should bemade in such a manner to be minimally invasive. As referred to herein,the term minimally invasive means in a manner by which an interior organor tissue may be accessed with as little as possible damage being doneto the anatomical structure through which entry is sought. Typically, aminimally invasive procedure is one that involves accessing a bodycavity by a small incision of, for example, approximately 5 cm or lessmade in the skin of the body. The incision may be vertical, horizontal,or slightly curved. If the incision is placed along one or more ribs, itshould follow the outline of the rib. The opening should extend deepenough to allow access to the thoracic cavity between the ribs or underthe sternum and is preferably set close to the rib cage and/ordiaphragm, dependent on the entry point chosen.

In one example method, the heart may be accessed through one or moreopenings made by a small incision(s) in a portion of the body proximalto the thoracic cavity, for example, between one or more of the ribs ofthe rib cage of a patient, proximate to the xyphoid appendage, or viathe abdomen and diaphragm. Access to the thoracic cavity may be soughtto allow the insertion and use of one or more thorascopic instruments,while access to the abdomen may be sought to allow the insertion and useof one or more laparoscopic instruments. Insertion of one or morevisualizing instruments may then be followed by transdiaphragmaticaccess to the heart. Additionally, access to the heart may be gained bydirect puncture (e.g., via an appropriately sized needle, for instancean 18-gauge needle) of the heart from the xyphoid region. Accordingly,the one or more incisions should be made in such a manner as to providean appropriate surgical field and access site to the heart in the leastinvasive manner possible. Access may also be achieved using percutaneousmethods further reducing the invasiveness of the procedure. See, forinstance, “Full-Spectrum Cardiac Surgery Through a Minimal IncisionMini-Sternotomy (Lower Half) Technique,” Doty et al., Annals of ThoracicSurgery 1998; 65(2): 573-7 and “Transxiphoid Approach Without MedianSternotomy for the Repair of Atrial Septal Defects,” Barbero-Marcial etal., Annals of Thoracic Surgery 1998; 65(3): 771-4, the entiredisclosures of each of which are incorporated herein by reference.

Once a suitable entry point has been established, the surgeon can useone or more sutures to make a series of stiches in one or moreconcentric circles in the myocardium at the desired location to create a“pursestring” closure. The Seldinger technique can be used to access theleft ventricle in the area surrounded by the pursestring suture bypuncturing the myocardium with a small sharp hollow needle (a “trocar”)with a guidewire in the lumen of the trocar. Once the ventricle has beenaccessed, the guidewire can be advanced, and the trocar removed. Avalved-introducer with dilator extending through the lumen of thevalved-introducer can be advanced over the guidewire to gain access tothe left ventricle. The guidewire and dilator can be removed and thevalved-introducer will maintain hemostasis, with or without a suitabledelivery device inserted therein, throughout the procedure.Alternatively, the surgeon can make a small incision in the myocardiumand insert the valved-introducer into the heart via the incision. Oncethe valved-introducer is properly placed the pursestring suture istightened to reduce bleeding around the shaft of the valved-introducer.

A suitable device such as a delivery device described in the '761 PCTApplication and/or the '170 PCT Application, may be advanced into thebody and through the valved-introducer in a manner to access the leftventricle. The advancement of the device may be performed in conjunctionwith sonography or direct visualization (e.g., direct transbloodvisualization). For example, the delivery device may be advanced inconjunction with TEE guidance or ICE to facilitate and direct themovement and proper positioning of the device for contacting theappropriate apical region of the heart. Typical procedures for use ofecho guidance are set forth in Suematsu.

As shown in FIG. 6, one or more chambers, e.g., the left atrium 12, leftventricle 14, right atrium 16, or right ventricle 18 in the heart 10 maybe accessed in accordance with the methods disclosed herein. Access intoa chamber 12, 14, 16, 18 in the heart 10 may be made at any suitablesite of entry but is preferably made in the apex region of the heart,for example, slightly above the apex 26 at the level of the papillarymuscles 19 (see also FIG. 5C). Typically, access into the left ventricle14, for instance, to perform a mitral valve repair, is gained throughthe process described above performed in the apical region, close to (orslightly skewed toward the left of) the median axis 28 of the heart 10.Typically, access into the right ventricle 18, for instance, to performa tricuspid valve repair, is gained through the process described aboveperformed in the apical region, close to or slightly skewed toward theright of the median axis 28 of the heart 10. Generally, an apex regionof the heart is a bottom region of the heart that is within the left orright ventricular region and is below the mitral valve 22 and tricuspidvalve 24 and toward the tip or apex 26 of the heart 10. Morespecifically, an apex region AR of the heart (see, e.g., FIG. 6) iswithin a few centimeters to the right or to the left of the septum 20 ofthe heart 10 at or near the level of the papillary muscles 19.Accordingly, the ventricle can be accessed directly via the apex 26, orvia an off-apex location that is in the apical or apex region AR, butslightly removed from the apex 26, such as via a lateral ventricularwall, a region between the apex 26 and the base of a papillary muscle19, or even directly at the base of a papillary muscle 19 or above.Typically, the incision made to access the appropriate ventricle of theheart is no longer than about, for example, about 0.5 cm. Alternatively,access can be obtained using the Seldinger technique described above.

The mitral valve 22 and tricuspid valve 24 can be divided into threeparts: an annulus (see 53 in FIGS. 5A and FB), leaflets (see 52, 54 inFIGS. 5A and 5B), and a sub-valvular apparatus. The sub-valvularapparatus includes the papillary muscles 19 (see FIG. 4) and the chordaetendineae 17 (see FIG. 4), which can elongate and/or rupture. If thevalve is functioning properly, when closed, the free margins or edges ofthe leaflets come together and form a tight junction, the arc of which,in the mitral valve, is known as the line, plane, or area of coaptation.Normal mitral and tricuspid valves open when the ventricles relaxallowing blood from the atrium to fill the decompressed ventricle. Whenthe ventricle contracts, chordae tendineae properly position the valveleaflets such that the increase in pressure within the ventricle causesthe valve to close, thereby preventing blood from leaking into theatrium and assuring that all of the blood leaving the ventricle isejected through the aortic valve (not shown) and pulmonic valve (notshown) into the arteries of the body. Accordingly, proper function ofthe valves depends on a complex interplay between the annulus, leaflets,and sub-valvular apparatus. Lesions in any of these components can causethe valve to dysfunction and thereby lead to valve regurgitation. As setforth herein, regurgitation occurs when the leaflets do not coaptproperly at peak contraction pressures. As a result, an undesired backflow of blood from the ventricle into the atrium occurs.

Although the procedures described herein are with reference to repairinga cardiac mitral valve or tricuspid valve by the implantation of one ormore artificial chordae, the methods presented are readily adaptable forvarious types of tissue, leaflet, and annular repair procedures. Themethods described herein, for example, can be performed to selectivelyapproximate two or more portions of tissue to limit a gap between theportions. In general, the methods herein are described with reference toa mitral valve 22 but should not be understood to be limited toprocedures involving the mitral valve.

Example Devices for Approximating Tissues

FIG. 7 illustrates a block diagram of an example LS delivery device 846having a knot holder 841 and atraumatic tip 840 with a tensioner 843 andrelease mechanism 842. The LS delivery device 846 is configured tosecure a pre-formed locking suture to allow one or more suture ends tobe passed through or interweaved with the locking suture, to maneuverthe locking suture with suture ends to a targeted location, to allow thesuture ends to be adjusted, to tension the locking suture to lock thesuture ends (e.g., to inhibit relative motion between the suture tailsand the locking suture), and to release the locking suture in itsdeployed or locked state.

The LS delivery device 846 includes the atraumatic tip 840 attached tothe knot holder 841. The atraumatic tip 840 can be the most distalcomponent of the LS delivery device 846 so that as the LS deliverydevice 846 advances the locking suture little or no damage is done tothe tissue in the target region, such as a valve leaflet. The atraumatictip 840 can be made of a tissue-friendly material that is pliable and/orrelatively dull to prevent or reduce the likelihood of tissue damagewhen the LS delivery device 846 is in the process of delivering thelocking suture to its targeted location.

The knot holder 841 is configured to secure the locking suture in itspre-deployment or delivery configuration. The knot holder 841 can be aneedle holder and/or a knot holder, where the needle holder secures aneedle that is used to hold or secure the locking suture in place duringa portion of a procedure using the locking suture. For example, a needlecan be used to hold a locking suture while suture tail ends areinterweaved or inserted through the locking suture, after which theneedle can be removed leaving the locking suture with the suture tailends in a delivery configuration. An example of this configuration isdescribed herein with reference to FIGS. 18A-18K.

The knot holder 841 can be configured to push off the locking suture aspart of deployment or the transition from a delivery state to a deployedstate. The knot holder 841 can be configured to pull back the holder sothat the locking suture slides off the LS delivery device 846. Forexample, the knot holder 841 can include an outer tube with a flexiblefeature at a distal end (where the flexible feature functions as theatraumatic tip 840). In some embodiments, the LS delivery device 846 cansecure a loose locking suture or a locking suture in a deliveryconfiguration that allows suture tail ends to be threaded through thelocking suture using the knot holder 841 wherein the knot holderincludes a needle holder. Once the locking suture and suture tail endsare sufficiently intertwined, the needle holder can be removed leavingthe locking suture secured to the flexible distal end of the outer tubefor delivery.

In some embodiments, the knot holder 841 secures the knot in placewithout a tip 840 in such a way that the knot goes before the knotholder 841, the knot therefore providing protection against tissuedamage. In some embodiments, the knot holder 841 also includestissue-friendly characteristics so that the knot holder 841 and theatraumatic tip 840 are combined. An example of such a configuration isdescribed herein with reference to FIGS. 18A-18K (see, e.g., FIG. 18J).

The LS delivery device 846 includes a tensioner 843 that is configuredto apply tension to the ends of the locking suture to transition thelocking suture from a delivery configuration to a deployedconfiguration. The transition from the delivery configuration to thedeployed configuration includes tightening the locking suture to inhibitrelative motion between the locking suture and the suture tail ends.Examples of components of the tensioner 843 include, but are not limitedto, a pinion wheel, a loaded spring, gears, grips to allow manuallypulling the locking suture tethers, and the like.

The tensioner 843 is configured so that, advantageously, application oftension to a knot portion of the locking suture does not alter orincrease proximal tension on suture tail ends intertwined with the knotportion. For example, the knot holder 841 can be configured so that thetensioner 843 applies force to a tether portion of the locking sutureand the knot holder 841 directs the applied force to cause the knotportion to tighten while not pulling proximally on the suture tail ends.This can be accomplished, at least in part, by fixing the knot portionin place with the knot holder 841 while it is being tightened. This canbe accomplished, at least in part, by configuring the knot holder 841 sothat it re-directs tension on the tether portion at an angle relative tothe knot portion of the locking suture.

The tensioner 843 can be configured to provide mechanical advantageswhen tensioning the tethers of the locking suture. For example, thetensioner 843 can be configured to provide a targeted tension. Asanother example, the tensioner 843 can be configured to prevent orinhibit the application of too much force to prevent over-tensioning thelocking suture. The tensioner 843 may include one or more sensorsconfigured to determine or measure the amount of tension on the lockingsuture tethers. The tensioner 843 may also include feedback systems oruser interface features to indicate when a targeted tension has beenachieved (or exceeded). Examples include gauges, readouts, indicatorlights (e.g., green, yellow, and red lights), and the like. Thetensioner 843 may include a mechanism for allowing a user to dial, set,or enter a targeted tension. The tensioner 843 can then provide thattargeted tension to improve repeatability and reliability of the LSdelivery device 846.

The tensioner 843 can be a multi-stage device that provides forces atdifferent times. For example, the tensioner 843 can be configured tosequentially tension or apply force to the ends of the locking suture.As another example, the tensioner 843 can be configured to apply a firstforce to a first locking suture end (e.g., a first tether) and at alater time to apply a second force to a second locking suture end (e.g.,a second tether). In this way, the tensioner can be configured to applya targeted force to each tether of the locking suture to achieve atargeted locking force on the suture tail ends. In some embodiments, thetensioner 843 is configured to apply at least about 5 N and/or less thanor equal to about 40 N, at least about 7 N and/or less than or equal toabout 35 N, or at least about 10 N and/or less than or equal to about 30N on an individual tether of the locking suture. In some embodiments,prior to deployment, the locking suture can be configured to slide alongthe suture tails with the application of at least 3 N of force and/orless than or equal to about 13 N of force, at least 4 N of force and/orless than or equal to about 10 N of force, or at least 5 N of forceand/or less than or equal to about 7.5 N of force.

The LS delivery device 846 also includes a release mechanism 842. Therelease mechanism 842 is configured to cause the knot holder 841 torelease the locking suture after it has transitioned to a deployedstate. The release mechanism 843 is configured to interface or interactwith the tensioner 843 and/or the knot holder 841 to cause thesecomponents to release the locking suture. The release mechanism 842 canbe manually activated by a user or it can be configured to automaticallyrelease the locking suture after the locking suture has been tightenedby the tensioner. In some embodiments, the release mechanism 842includes one or more user interface features to allow the user tocontrol when the release mechanism 843 releases the locking suture andsuture tail ends.

Example Methods of Approximating Tissues

FIG. 8 illustrates a flow chart of an example method 900 for securing alocking suture to approximate distal anchors attached to tissue. Themethod 900 can be used with any of the LS delivery devices disclosedherein. The method 900 can be used to approximate any tissue that canreceive an anchor implant (e.g., a bulky knot implant) with a sutureattached thereto. Examples provided herein focus on implantingartificial tendineae, but other procedures may utilize the method 900.Where the term anchor is used herein, it is to be understood that ananchor refers to any suitable component or element that serves to anchora suture to tissue such as, for example and without limitation, hooks,barbs, knots (e.g., bulky knots), and the like.

In some embodiments, the method 900 improves upon existing Alfieriprocedures by sliding a locking suture to adjust the tension anddirection of force vectors applied to tissues to be approximated.Advantageously, the method 900 allows an operator (e.g., a physician orsurgeon) a way to change force vectors applied by anchor implants intissue. For example, when implanting artificial chordae tendineae, theknot that coalesces a plurality of the sutures or cords can be adjustedto be at any location from the apex of the heart to the valve with theimplanted cords. This can be used to adjust both the angle of the forcevectors as well as the magnitude of the force vectors, providingincreased control to the operator.

At step 905, two or more artificial cords are attached to targetedtissue. The artificial cords include anchor implants at a distal endthat are anchored to the targeted tissue, e.g., a posterior or anteriorleaflet. The cords also include sutures extending proximally from theanchor implants. These sutures extend proximally from the implants to aregion away and/or outside of the targeted region. In some embodiments,the targeted region is within the heart or within a chamber of the heart(e.g., the left ventricle).

At step 910, the proximal ends or portions of the sutures are threadedthrough a pre-formed locking suture. The sutures can be threaded throughvarious strands of the locking suture or the sutures can be threadedthrough a central lumen or corridor of the locking suture. The lockingsuture can be attached or secure to a LS delivery device, such as any ofthe LS delivery devices described herein. The LS delivery device can beconfigured to deploy and release the locking suture after approximationof the targeted tissue.

The pre-formed locking suture can be any of the locking suturesdescribed herein. In some embodiments, the pre-formed locking sutureincludes a knot formed from a suture wherein the knot includes aplurality of cow hitches with ends of the knot suture being threadedthrough portions of the plurality of cow hitches so that, when the endsof the knot suture are tensioned, they axially and radially constrict tocreate a tortuous path for any suture tail ends threaded through thelocking suture. In this way, the suture tail ends and the locking sutureare inhibited or prevented from relative movement.

At step 915, the locking suture with the suture tail ends intertwined ismoved along the sutures toward and/or away from the distal anchors andthe targeted tissue. Moving, sliding, or otherwise translating thelocking suture in its delivery configuration can be accomplished usingan LS delivery device. The device can push and pull the locking sutureto a targeted location. This can be monitored and confirmed usingvarious imaging techniques.

Moving the locking suture towards the targeted tissue causes theimplants (and the tissues) to approximate. By moving the locking suturedistally (e.g., pushing), the targeted tissue can be approximated.Similarly, by moving the locking suture proximally (e.g., pulling), theapproximation of the tissues can be decreased. Thus, the LS deliverydevice allows an operator to control approximation of the distal anchorsand, consequently, the targeted tissue.

In addition, sliding the locking suture along the suture tails causes apoint of intersection of the sutures to move closer to the targetedtissues. This adjusts the angles of the forces applied to the implants,and therefore to the tissue.

At optional step 917, the tension of the sutures can be adjusted. Thiscan be done, for example, by pulling proximally on the suture tail ends.This can be done in conjunction with sliding the locking suture totailor the force vectors on the implants to achieve targeted tissueapproximation. For example, sliding the locking suture can be donesimultaneously with pulling (or releasing tension) on the sutures toachieve targeted force vectors and/or targeted tissue approximation.

At step 920, imaging or other methods are used to verify that thetargeted approximation of the tissues has been achieved. This feedbackstep allows the operator to iteratively adjust the position of thelocking suture and/or the amount of tension on the sutures (e.g., asprovided in optional step 517). The iterative nature of this portion ofthe method 900 is illustrated using an arrow that goes from step 920back to step 915. Imaging methods include cardiac ultrasound and echoguidance, as described herein.

Once the targeted approximation of the targeted tissue has beenachieved, the locking suture is deployed at step 922. Deployment of thelocking suture includes applying tension to individual tethers of thelocking suture. As described herein, the tension can be applied atdifferent times (e.g., sequentially) and/or with different forces toachieve sufficient or targeted locking of the locking suture. The LSdelivery device can be used to tension the locking suture and release itafter tensioning. The LS delivery device can be configured so thattension applied to individual tethers of the locking suture does notalter or increase the tension on the distal anchors and the targetedtissue. For example, the knot portion can be secured in place by the LSdelivery device while tension is applied to the tether portion to limitor prevent movement of the knot portion relative to the two or moresutures during deployment of the locking suture.

At step 930, the locked sutures are anchored. The anchoring step is doneto prevent or to reduce the likelihood that the locked sutures will comeloose. The sutures can be anchored to a tissue wall, such as an externalwall of the heart. A pledget can be used as the anchor. For example,PTFE (Teflon®, DuPont, Wilmington, Del.) felt can be used as an anchorwhere the felt is attached to the tissue wall. In some embodiments, theanchor includes a plurality of holes through which the sutures extend.Knots and/or additional locking sutures can be used to anchor thesutures.

Advantageously, the locking suture is configured to be able to be movedor slid from outside of the target region. This can allow greateraccessibility and flexibility to operators performing the procedure.Another advantage of the method 900 is that it is adjustable. The method900 also allows for real-time adjustment of tissue approximation toachieve coaptation between leaflets because an operator can adjust thetension of the sutures, and by extension the approximation of theimplants and targeted tissue, based on feedback from a visualizationsystem (e.g., cardiac ultrasound).

The method 900 also provides other advantages over other approaches toaddressing MR. For example, implanting a clip in the mitral valve toaddress MR does not provide adjustability. In contrast, the method 900allows for real-time adjustability. Furthermore, the method 900 can beaccomplished using real-time imaging or other feedback to reduce oreliminate MR. This allows an operator to see the effects of theprocedure in real time allowing for the operator to make adjustments toachieve targeted results. In addition, if reoperation is required thevalve is unaffected by the method 900 whereas a mitral valve clip maydestroy or damage the tissue. Furthermore, a mitral valve clip is arelatively large amount of hardware to implant in the heart which mayincrease the risk of embolism and tissue rejection. With the method 900,the only materials implanted in the body are the sutures which present asignificantly lower risk to the patient.

Additional Example Locking Suture Delivery Devices and Methods

FIGS. 9 and 10A-10D illustrate schematically a method and deliverydevice for delivering and deploying a locking suture 337 to secureartificial chordae tendineae that have been implanted as described inthe '761 PCT Application and/or the '170 PCT Application. FIG. 9 is aschematic illustration of a mitral valve 322 with leaflets 352, 354 thatare separated by a gap 363. As shown in FIG. 9, two bulky knot implants331, 331′ are disposed on an atrial, distal, or top side of the leaflets352, 354, respectively. The implants 331, 331′ can be formed with asuture material that forms one or more loops on the atrial side of theleaflets 352, 354 and extends through the leaflets 352, 354, with twoloose suture end portions that extend on the ventricular, proximal, orbottom side of the leaflets 352, 354. The implant 331 has suture endportions 332 and 333, and the implant 331′ has suture end portions 334and 335 (not shown in FIG. 9).

After the implants 331, 331′ are in a desired or targeted position(which can be confirmed with imaging, for example), a LS delivery device346 as shown in FIGS. 10A-10D can be used during a procedure to securethe implants 331, 331′ in the desired position and to secure the valveleaflets 352, 354 in an edge-to-edge relationship. Further, in additionto or instead of creating the edge-to-edge relationship, to promote alarger surface of coaptation, using the LS delivery device 346, theimplants 331, 331′ can be secured together to pull or otherwise move theposterior annulus towards the anterior leaflet and/or the anteriorannulus towards the posterior leaflet, to reduce the distance betweenthe anterior annulus and the posterior annulus, e.g., the septal-lateraldistance by about 10%-40%. Approximating the anterior annulus and theposterior annulus in this manner can decrease the valve orifice, andthereby decrease, limit, or otherwise prevent undesirable regurgitation.This technique can be valuable in both degenerative MR with a prolapsedleaflet where the annulus is dilated and in functional MR where theleaflet function is normal but the annulus has dilated and there is agap between the leaflets that can be closed by approximating the tissue.

For ease of illustration, the following example locking suturedeployment sequence in connection with FIGS. 10A-10D is shown anddescribed using only two suture portions 332, 334. Note, however, thelocking suture can be deployed about and secured to any suitable numberof suture portions. For example, as shown in or described with respectto FIG. 9, four suture portions (e.g., sutures portions 332, 333, 334,335) extend from the implants 331, 331′. Further, in some embodiments,in which more than two implants and/or more than two tissues are to beapproximated, the locking suture can be deployed about and/or secured tomore than four suture portions (e.g., six or more suture portions).

As shown in schematic cross-section in FIG. 10A, the LS delivery device346 includes a distal end portion 340, a medial portion 338, and aproximal end portion 336. Disposed on the distal end portion 340 is aknot end effector 333 that extends from a distal end portion 340 of anelongated knot pusher tube 347 (also referred to herein as “knotpusher”). As described in further detail below, the knot end effector333 provides a surface against which and/or a volume within which a knotportion 337A of the locking suture 337 can be deployed. A proximal endportion of the knot pusher 347 is coupled to a handle 335 at theproximal end portion 336 of the LS delivery device 346. Coupled to andincluded at least partially within the handle 335 is a proximal endportion of the knot pusher 347 coupled to a pusher hub 357, an innerelongate member 341 (also referred to herein as “pre-formed knot holder”or “knot holder”) coupled to an inner elongate member hub 351 (alsoreferred to herein as “knot holder hub”), and a locking suture catch 367(also referred to herein as “LS catch”). As shown, the knot holder hub351 is disposed proximal to the knot pusher hub 357 and distal to the LScatch 367. The knot holder 341 is movably disposed within a lumen of theknot pusher 347. As shown in FIG. 10A, the locking suture 337 is coupledto the LS catch 367 and extends through a lumen of the knot holder 341and a lumen of the knot pusher 347 and is formed into a coiledconfiguration (e.g., the knot portion 337A) at the distal end portion340 of the LS delivery device 346. More specifically, the knot portion337A of the locking suture 337 is disposed about the distal end portionof the knot holder 341 and distal to the knot pusher 347, and the tetherportion 337B of the locking suture 337 extends from the knot portion 337through the lumen of the knot pusher 347 and coupled to the LS catch 367within the handle 335.

The LS catch 367 can be configured to releasably hold or secure thetether portion 337B during delivery and deployment of the knot portion337A as described in more detail below. In some embodiments, the LScatch 367 can hold the tether portion 337B with a friction fit or with aclamping force and can have a lock that can be released after the knotportion 337A has been deployed. As discussed above for locking suture337, for example, the knot portion 337A can be in the form of one ormore multi-turn coils, winds, and/or cow hitches of the locking suture337 that can be changed from an elongated configuration during delivery(see, e.g., FIGS. 10A and 10B), to a deployed configuration (e.g.,tightened, bulky, bunched, or looped knot; see, e.g., FIG. 10D) bytightening, constricting, and/or shrinking the multi-turn coils orwinds, and/or approximating opposite ends of the winds or coils towardseach other. Said another way, during deployment, the coils, wraps,loops, turns, or portions of the knot portion 337A disposed about thesuture portions 332, 334 are tightened, shortened, and/or constricted,and/or looped resulting in a restrained or confined tortuous path forthe suture portions 332, 334 sufficient to inhibit relative motionbetween the knot portion 337A and the regions of the suture portions332, 334 intertwined therewith.

To deliver and deploy the locking suture 346 to suitably approximate thesuture portions 332, 334 and implants 331, 331′, and the heart tissuesT1, T2 (the implants and heart tissues are not shown in FIGS. 10A-10D)attached thereto, for example, the free ends of the suture portions 332,334 extending from the implants 331, 331′ inside the heart and throughan incision in the apex region of the heart, for example, can bethreaded, woven, and/or routed through the turns or winds of the knotportion 337A, e.g., in FIG. 8B. As shown and described in furtherembodiments below, the LS delivery device 346 in some instances may bepre-loaded with one or more wire threaders (not shown in thisembodiment) to assist an operator (e.g., a surgeon) with threading thesuture portions 332, 334 through various regions of the knot portion337A in a desired and/or predefined configuration to maximizepost-deployment securement between the suture portions 332, 334 and thelocking suture 337.

With the suture portions 332, 334 suitably threaded through and/orcoupled to the knot portion 337 (in its delivery configuration), asshown in FIG. 10B, the free ends of the suture portions 332, 334 can bereleasably held by the operator and/or releasably fixed or secured to asuitable component (e.g., to a portion of the knot pusher 347). With thefree ends of the suture portions 332, 334 releasably fixed in thismanner, the LS delivery device 346 can be advanced distally relative tothe fixed free ends of the suture portions 332, 334 and towards theheart tissues and to a suitable deployment location, similar to as shownand described with respect to FIG. 2B. For example, the distal endportion 340, and in some instances the medial portion 338, of the LSdelivery device 346 can be moved distally through the incision (throughwhich the suture portions 332, 334 extend from the heart) and into theleft ventricle of the heart. In this manner, the knot portion 337A canbe advanced along or about the suture portions 332, 334 and towards thetissues until the knot portion 337A reaches a desirable location and/orthe tissues are desirably approximated.

With the knot portion 337A delivered to a suitable location and/or withthe tissues desirably approximated, the knot holder hub 351 can bewithdrawn within and relative to the handle 335 (in the direction ofarrow B) and/or the knot pusher hub 357 can be pushed or moved distallywithin and relative to the handle 335 (in the direction of arrow A) todisplace the knot portion 337A off and/or from the knot holder 341,leaving the knot portion 337A separate from the knot holder 341 and onthe distal side of the knot pusher 351, as shown in FIG. 10C. In someinstances, there can be some slack in the length of tether portion 337Bto allow the knot portion 337A to slide off the knot holder 341 beforedeploying. With the knot portion 337A displaced from the knot holder341, the knot portion 337 is ready to be deployed about the sutureportions 332, 334 threaded therethrough. To deploy, the knot holder hub351 and the LS catch 367, and thereby the tether portion 337B of thelocking suture 337 (which is releasably fixed to the LS catch 367), canbe withdrawn proximally within and relative to the handle 335 (in thedirection of arrow C), causing the knot portion 337A to transition fromits delivery configuration to its deployed configuration, as shown inFIG. 10D. Although in this embodiment at this stage the LS catch 367 andthe knot holder hub 351 are shown and described as being withdrawnwithin the handle 335 together, in other embodiments, the LS catch 367can be withdrawn proximally relative to the knot holder hub 351 todeploy the knot portion 337A of the locking suture 337. Morespecifically, with the tether portion 337B releasably secured to the LScatch 367, proximal movement of the LS catch 367 relative to the knotpusher pulls the tether portion 337B proximally, causing the knotportion 337A to deploy on the distal end of the knot pusher 347.

After the knot portion 337A has been deployed (FIG. 10D), the sutureportions 332, 334 can be released by the operator, and the tetherportion 337B can be released from the LS catch 367, and the LS deliverydevice 346 can be withdrawn proximally in the direction of arrow D,leaving the deployed knot portion 337A within the heart, and free endsof the suture portions 332, 334 and the free ends of the tether portion337B extending out of the heart. In other words, with the tether portion337B released from the LS catch 367 and the two lengths of the sutureportions 332, 334 extending proximally from the deployed knot portion337A similarly released, the LS delivery device 346 can be slid over thetwo lengths of the suture portions 332, 334 for removal.

The locking suture, and particularly the knot portions described herein(e.g., knot portion 137A, 237A, 337A) can be formed in any suitableformation such that the locking suture can be suitably delivered anddeployed in various expected environments, and that when deployed withportions of one or more sutures (e.g., suture portions 332, 333, 334,335) threaded therethrough, the deployed knot portion will secure and/orinhibit relative movement between the deployed knot portion and thesutures disposed or captured therein. In this manner, similar to asdescribed with respect to FIG. 2D and locking suture 237, securing orinhibiting relative movement can promote a desirable approximation ofthe tissues attached to the deployed knot portion via the sutureportions.

There are several design considerations for the knot portion. Whendisposed about the knot holder, unraveling of the knot portion can beinhibited or prevented during delivery to a target region. The knotportion can be assembled about the knot holder without fastening orretaining means (e.g., retaining clips or bands) to hold the knotportion in place without unraveling, thus promoting more efficientassembly. When disposed about the knot holder, suture portions extendingfrom the tissues can glide or be threaded through the winds or coils ofthe knot portion with minimal resistance to promote efficient assembly.When deployed about the suture portions, the knot portion inhibitsrelative movement therebetween, and the knot portion retains thisdeployed state in part in response to tensile loading applied to itstether portion (e.g., the tether portion is pulled and anchored to anouter surface of the heart at a desirable tension). Slack or loose coilsor winds in the knot portion from assembly to delivery and deploymentcan be inhibited or prevented. The knot portion is suitably slidablealong or about the suture portions during delivery, including outsidethe target region or patient (e.g., in a relatively dry environment) andinside the target region or patient (e.g., in a relatively wetenvironment, such as, for example, within a beating heart). The knotportion is deliverable through an introducer or delivery catheterwithout being compromised (e.g., unraveling; damaged, or any otherundesirable consequences). The knot portion is capable of being guidedalong or about the sutures without undesirable tension on the tissuesattached to the sutures, by for example, pulling or tensioning thesutures while the knot portion is guided along or about the suture. Theknot portion is capable of maintaining its deployed state under expectedpressures or tension, such as, for example, about 2.2 pounds per squareinch (psi).

FIGS. 11A-11G illustrate an example method of forming a knot portion437A of a locking suture 437 in an elongated coiled configuration (e.g.,delivery configuration) about an exterior of a knot holder 441. Thelocking suture 437 and the knot holder 441 can be constructed similarlyto or the same as, and function similarly to or the same as, any of thelocking sutures and knot holders described herein. Thus, some detailsregarding the locking suture 437 and the knot holder 441 are notdescribed below. It should be understood that for features and functionsnot specifically discussed, those features and functions can be the sameas or similar to any of the locking sutures and knot holders describedherein.

To begin formation of the knot portion 437A, in this embodiment, asshown in FIGS. 11A-11C, three cow hitches 437A-1, 437A-2, 437A-3 areformed about the knot holder 441. Although in this embodiment three cowhitches are used, in alternative embodiments, any suitable number of cowhitches may be used (e.g., 1, 2, 4, 5, or more cow hitches). The numberof cow hitches may be selected based on the particular medical operationand/or the forces that the deployed locking suture 437 is expected toexperience. For approximating two tissues within a ventricle of a humanheart, for example, it has been found that, in some instances, three cowhitches is sufficient. For ease of illustration, the locking suture 437is illustrated with each loop formed about the knot holder 441 beinglabeled from loop 1 through loop 6 (from left to right, or distal toproximal). Each cow hitch defines two loops. Specifically, first cowhitch 437A-1 defines loop 1 and loop 2, second cow hitch 437A-2 definesloop 3 and loop 4, and third cow hitch 437A-3 defines loop 5 and loop 6,as illustrated and labeled in FIGS. 11D-11G. After the three cow hitchesare formed, the first free end extending from the first cow hitch 437A-1(see, e.g., FIG. 11C in which the first free end is hatched in green,which is an extension of the white portion extending from loop 1 of thefirst cow hitch 437A-1) is routed proximally and threaded through loop 3and loop 5, as shown in FIG. 11D. More specifically, as shown in FIG.11D, the first free end is routed around (or over, or radially outwardlyfrom) loop 2, then through (or within, or radially inwardly from) loop3, then around loop 4, then through loop 5, and then around loop 6.After exiting loop 6, the first free end is wrapped or turned aroundloop 6, as shown in FIG. 11F. Similarly stated, after exiting loop 6,the first free end is routed distally through loop 6 for a second timeand then proximally around loop 6 for a second time.

Additionally, after the three cow hitches are formed, the second freeend (e.g., the other free end of the locking suture 437) extending fromthe first cow hitch 437A-1 is routed proximally and threaded throughloop 4 and loop 5, as shown in FIG. 11E. More specifically, as shown inFIG. 11E, the second free end is routed around loop 3, then through loop4 and loop 5, and then around loop 6. After extending through loop 4 and5 and around loop 6, the second free end is wrapped or turned aroundloop 5 (e.g., through and around loop 5), and then through loop 6, asshown in FIG. 11G.

FIGS. 12A-12E illustrate another example approach for forming thelocking suture knot 437. FIG. 12A illustrates an alternate proceduralstep after performing the step illustrated in FIG. 11D. Thus, in FIG.12A the second free end is routed around loop 3, then through loops 4,5, and 6. After extending through loops 4, 5, and 6, the second free endis brought back through loops 5 and 6, as illustrated in FIG. 12B. Thefirst free end is then looped under loop 6 so that it goes through theloop formed by the second free end in the previous step, as illustratedin FIG. 12C. The first free end is then looped back around to go overthe loop formed by the second free end and through loop 6, asillustrated in FIG. 12D. The resulting locking suture is tensioned toremove the slack while still allowing the locking suture to slide toallow it to be positioned along suture tails, as illustrated in FIG.12E.

FIGS. 13, 14, 15A-15I, 16A-16AL, and 17A-17W illustrate anotherembodiment of a LS delivery device 546 that can be used to deliver anddeploy a locking suture 537. The LS delivery device 546 and the lockingsuture 537 can be constructed similar to or the same as and functionsimilar to or the same as any of the LS delivery devices and lockingsutures described herein. Thus, some details regarding the LS deliverydevice 546 and the locking suture 537 are not described below. It shouldbe understood that for features and functions not specificallydiscussed, those features and functions can be the same as or similar toany of the LS delivery devices and locking sutures described herein.

As shown in FIGS. 13 (right side view) and 14 (left side view), the LSdelivery device 546 includes a distal end portion 540, a medial portion538, and a proximal end portion 536. Disposed on the distal end portion540 is a knot end effector 533 that extends from a distal end portion540 of an elongated knot pusher tube 547 (also referred to herein as“knot pusher”). As described in further detail below, the knot endeffector 533 provides a surface against which, and a volume withinwhich, a knot portion 537A of the locking suture 537 can be deployed. Aproximal end portion of the knot pusher 547 is coupled to a handle 535at the proximal end portion 536 of the LS delivery device 546. Extendingfrom within the handle 535, through a lumen of the knot pusher 547, andout a distal end of the knot end effector 533 is an inner elongatemember 541 (also referred to herein as “pre-formed knot holder” or “knotholder”). The knot holder 541 is slidably disposed within the knotpusher 547 and the handle 535, and is retractable (relative to the knotpusher 547 and handle 535) from the position shown in FIGS. 13 and 14 inwhich the distal end of the knot holder 541 is distal to the knot endeffector 533 to a position (not shown) in which the distal end of theknot holder 541 is proximal to the knot end effector 533. In thismanner, as described in previous embodiments, in use, the knot portion537A can be formed about the distal end of the knot holder 541 in aposition distal to the knot end effector 533, and then delivered to asuitable location within a target region (e.g., within the leftventricle of a heart). The LS delivery device 546 can then be actuatedto deploy the knot portion 537A, which can include displacing the knotportion 537A from the knot holder 541 by retracting or withdrawingproximally the knot holder 541 relative to the knot pusher 547.

Although in this embodiment the knot holder 541 is described as beingslidable within and relative to the knot pusher 547 and the handle 533,in other embodiments, an LS delivery device can be constructed in anysuitable manner to displace a knot portion from a knot holder. In suchalternative embodiments, for example, an LS delivery device may includea knot holder fixed relative to and extending from its handle, and aknot pusher slidable or extendable from the handle sufficient to push ordisplace the knot portion from and distal to the fixed knot holder.

The LS delivery device 546 further includes an actuator 557 (alsoreferred to herein as a “plunger”) configured to be actuated to push oradvance the knot pusher 547 distally relative to the handle 533. Toprevent premature advancement of the plunger 557, the LS delivery device546 further includes a plunger lock 559 configured to be manipulatedbetween a locked position, in which movement of the plunger 557 relativeto the handle 533 is inhibited or prevented, and an unlocked position,in which the plunger 557 can be moved (e.g., actuated) relative to thehandle 533. Similarly the stated, the plunger 557 cannot be actuatedwhen the plunger lock 559 is in its locked position, and can be actuatedwhen the plunger lock 559 is in its unlocked position.

Further, to prevent undesirable retraction or proximal movement of theplunger 557 (which could undesirably expose the distal end of the knotholder 541 from the distal end of the knot pusher 547), for example,after displacement of the knot portion 537A from the knot holder anddistal advancement or actuation of the plunger 557, the LS deliverydevice 546 further includes a plunger retainer 549 configured to beengaged or transitioned to its retaining position to prevent undesirableproximal movement of the plunger 557 relative to the handle 533.

FIGS. 15A and 15C illustrate detailed top and side views, respectively,of the knot pusher 547, the knot end effector 533, and the knot holder541 extending distally therefrom. FIG. 15B illustrates a detailed topview of the knot pusher 547 and the knot end effector 533, but with thedistal end of the knot holder 541 disposed within the lumen of the knotpusher 547 and proximal to the knot end effector 533. FIG. 15Dillustrates a detailed front view of the knot pusher 547, the knot endeffector 533, and the knot holder 541 disposed within the lumen of theknot pusher 547. FIG. 15E illustrates a detailed perspective view of theknot pusher 547, the knot end effector 533, and the knot holder 541extending distally therefrom. FIG. 15F illustrates a detailed front viewversion of FIG. 15E; FIG. 15G illustrates a detailed bottom perspectiveview version of FIG. 15E; FIG. 15H illustrates a detailed top viewversion of FIG. 15E; and FIG. 15I illustrates a detailed frontperspective view version of FIG. 15E.

The knot end effector 533 includes a knot receiving portion 533A (alsoreferred to herein as “end effector cup”) configured to provide a volumeor partial enclosure within which the knot portion 537A can be deployed,and/or a surface or backstop against which the knot portion 537A can bedeployed. Similarly stated, the end effector cup 533A can serve as aplace holder for the knot portion 537A to form during deployment. Inthis manner, the end effector cup 533A can contain the knot portion 537Aand inhibit undesirable movement, for example, as the free ends ortether portion 537A is tensioned, pulled, and/or withdrawn. In use, forexample, when the tether portion 537B is withdrawn to cause the knotportion 537A to deploy, the knot portion 537A in response to withdrawalof the tether portion 537B will be pulled or urged proximally into andagainst the knot receiving portion 533A. With the knot portion 537Awithin the knot receiving portion 533A and abutting a surface of theknot receiving portion 533A, further withdrawal of the tether portion537B will result in the coils and turns of the knot portion 537Atightening and constricting and the ends of the coils approximating, asdescribed in previous embodiments. Causing the knot portion 537A todeploy in such a restricted space (e.g., the partial enclosure of theknot receiving portion 533A) promotes formation of a sufficiently tightand secured deployed knot.

The knot end effector 533 further includes a protrusion 533B extendingdistally from the knot receiving portion 533A and configured to preventthe knot portion 537A from bunching and/or being drawn too far into thelumen of the knot pusher 547, for example, when the suture portionsextending from the tissues and implants (as described with respect toprevious embodiments) are threaded through the knot portion 537A andthen into the knot pusher 547, and to provide ample space through whichthe tether portion 537B can extend from the knot portion 537A into thelumen of the knot pusher 547 (see, e.g., FIG. 16AH). In some instances,the protrusion 533B is configured to partially displace the knot portion537A from the lumen of the knot pusher 547 to inhibit undesirableresistance for the suture portions when threaded and/or pulled throughportions of the knot portion 537A when in its delivery configuration.

The knot end effector 533 further includes an alignment loop, slot orguide 533C configured to slidably receive and at least partially align,guide, or retain the suture portions extending from the knot portion533A (see, e.g., FIG. 16AJ or FIGS. 15E, 15F, and 15I), as described infurther detail below. Further, the knot pusher 547 defines three sideapertures or orifices (e.g., a first aperture 547A, a second aperture547B circumferentially adjacent to the first aperture, and a thirdaperture 547C proximal to the first and second apertures 547A, 547B)proximal to the knot end effector 533, as shown in FIGS. 15A and 15B toprovide knot pushing functionality, as described in further detailbelow.

FIGS. 16A-16AK illustrate an example method of forming the knot portion537A in its delivery configuration (or “ready-state”) about the exteriorof the knot holder 541 and preparing the locking suture 537 and sutureportions for deployment. To begin formation of the knot portion 537A, inthis embodiment, as shown in FIGS. 16A-16C, three cow hitches 537A-1,537A-2, 537A-3 are formed about the knot holder 541 extending distallyfrom the knot end effector 533.

Although in this embodiment three cow hitches are used, in alternativeembodiments, any suitable number of cow hitches may be used (e.g., 1, 2,4, 5, or more cow hitches). The number of cow hitches may be selectedbased on the particular medical operation and/or the forces that thedeployed locking suture 537 is expected to experience. For approximatingtwo tissues within a ventricle of a human heart, for example, it hasbeen found that, in some instances, three cow hitches is sufficient. Forease of illustration, each loop formed about the knot holder 541 islabeled and/or referred to as loop 1 through loop 6 (from left to right,or distal to proximal). Each cow hitch defines two loops. Specifically,the first cow hitch 537A-1 defines loop 1 and loop 2, the second cowhitch 537A-2 defines loop 3 and loop 4, and the third cow hitch 537A-3defines loop 5 and loop 6, as illustrated and labeled in FIGS. 16C and16D. After the three cow hitches are formed, a wire threader 570 is usedto thread the free ends of the locking suture 537 to further form theknot portion 537. Specifically, as shown in FIG. 16D, the wire threader570 is inserted through loop 3 and loop 5, and then, as shown in FIG.16E, the first free end extending from loop 1 of the first cow hitch537A-1 is threaded through a loop of the wire threader 570. Next, thewire threader 570 is withdrawn from loops 3 and 5, thereby threading orpulling the first free end through loops 3 and 5, as shown in FIG. 16F.

Further, as shown in FIG. 16G, the wire threader 570 is inserted throughloop 4 and loop 5, and then, as shown in FIG. 16H, the second free endof the locking suture 537 extending from loop 2 of the first cow hitch537A-1 is threaded through the loop of the wire threader 570. Next, thewire threader 570 is withdrawn from loops 4 and 5, thereby threading orpulling the second free end through loops 4 and 5, as shown in FIG. 16I.FIG. 16J illustrates the knot portion 537A after the first free end isthreaded through loops 3 and 5 and the second free end is threadedthrough loops 4 and 5, as described above.

Next, the wire threader 570 is inserted through loop 5 and loop 6, asshown in FIG. 16K, and then, as shown in FIG. 16L, the first free end ofthe locking suture 537 is threaded through the loop of the wire threader570. Next, the wire threader 570 is withdrawn from loops 5 and 6,thereby threading or pulling the first free end through loops 5 and 6,as shown in FIGS. 16M and 16N.

Further, as shown in FIG. 160, the wire threader 570 is inserted throughloop 6 proximally, and then, as shown in FIG. 16P, the second free endof the locking suture 537 is threaded through the loop of the wirethreader 570. Next, the wire threader 570 is withdrawn distally fromloop 6, thereby threading or pulling the second free end through loop 6distally, as shown in FIGS. 16Q and 16R.

With the knot portion 537A formed about the knot holder 541, as shown inFIG. 16R, the free ends can be threaded through the knot pusher 547.Specifically, as shown in FIG. 16S, the wire threader 570 is inserteddistally through the first aperture 547A, and then, as shown in FIG.16T, the first free end of the locking suture 537 is threaded throughthe loop of the wire threader 570. Next, the wire threader 570 iswithdrawn proximally from the first aperture 547A, thereby threading orpulling the first free end of the locking suture 537 through the firstaperture 547A, as shown in FIG. 16U. Similarly, as shown in FIG. 16V,the wire threader 570 can be inserted distally through the secondaperture 547B, and then, as shown in FIG. 16W, the second free end ofthe locking suture 537 is threaded through the loop of the wire threader570. Next, the wire threader 570 is withdrawn proximally from the secondaperture 547B, thereby threading or pulling the second free end of thelocking suture 537 through the second aperture 547B, as shown in FIG.16X.

Next, a wire threader 573 is inserted distally into and through theproximal end portion (not shown) of the knot pusher 547, through thelumen of the knot pusher 547, and exiting the third aperture 547C, asshown in FIG. 16Y. Note that as shown the wire threader 573 is longerthan the wire threader 570 because the wire threader 573 needs to belong enough to extend through the length of the knot pusher from itsproximal end to the third aperture 547C (in some instances, a singlewire threader can be configured to be used to perform the functionsdescribed herein with respect to both the wire threader 570 and 573).With the loop of the wire threader 573 extending from within the lumenof the knot pusher 547 and through the third aperture 547C, both thefirst free end and the second free end of the locking suture 537 arethreaded through the loop of the wire threader 573, as shown in FIG.16Z, and then the wire threader 573 is withdrawn or pulled proximallythrough the lumen of the knot pusher 547, thereby threading both thefirst free end and the second free end of the locking suture 537 (e.g.,the tether portion 537B) proximally from the knot portion 537A into andthrough the lumen of the knot pusher 547, as shown in FIG. 16AA. Withthe tether portion 537B threaded into the third aperture 547C andproximally through the lumen of the knot pusher 547, the tether portion537B can be secured or fixed to the LS catch 567 (not shown in FIG.16AA).

Next, the knot portion 537A can be prepared to receive the sutureportions extending from the implants and tissues, as described inprevious embodiments, to assist the operator (e.g., surgeon) inthreading the free ends of the suture portions through particularportions of the knot portion 537A in a repeatable and efficient mannerwithout compromising the formation of the knot portion 537A. Forexample, as shown in FIG. 16AB, a first suture portion wire threader 571is inserted distally through loop 5, around loop 4 and loop 3, and thenthrough loop 2 and loop 1. Further, as shown in FIG. 16AC, a secondsuture portion wire threader 572 is inserted distally through loops 1-6,e.g., through loop 6, then loop 5, then loop 4, then loop 3, then loop2, and then loop 1.

At this stage, as shown in FIG. 16AC, the locking suture 537 is preparedto receive the suture portion, and then be delivered along or about thesuture portions to a suitable location within the target region fordeployment. In some embodiments, a kit can be provided to the operatorincluding any of the components described herein. For example, a kit mayinclude a knot holder and a locking suture 537 coupled thereto, withfirst suture portion wire threader 571 and second suture portion wirethreader 572 disposed through locking suture 537, as shown in FIG. 16AC.In some instances, the kit may include a LS delivery device assembledwith the locking suture, knot holder, and knot pusher, as illustrated invarious embodiments herein, while in on other instances, the kit mayinclude only portions of the LS delivery device, and/or multiple orduplicate components of the LS delivery device. For example, in someinstances, a kit may include a single handle and a single knot pusher,and multiple knot holders each having a locking suture coupled theretoin a delivery configuration, similar to as shown and described withrespect to FIG. 16AC. In this manner, an operator can deliver and deploymultiple locking sutures.

For example, as shown in FIG. 16AD, the operator (e.g., surgeon) canthread the free ends of the suture portions 532, 534 through the loop ofthe first suture portion wire threader 571, and then pull or withdrawproximally the first suture portion wire threader 571, thereby threadingthe free ends of the suture portions 532, 534 proximally through loops1-6, as shown in FIG. 16AE. Next, as shown in FIG. 16AF, the operatorcan thread the free ends of the suture portions 532, 534 through theloop of the second suture portion wire threader 572, and then pull orwithdrawn proximally the second suture portion wire threader 572,thereby threading the free ends of the suture portions 532, 534proximally through loops 1 and 2, around loops 3 and 4, and then throughloops 5 and 6, as shown in FIG. 16AG.

Next, while leaving some slack or length (e.g., about 1 to about 2inches) of the suture portions exposed at the distal end 540 of the LSdelivery device 546 (see, e.g., FIG. 16AH) the free ends of the sutureportions 532, 534 can be threaded proximally through the alignment loop,slot or guide 533C, and then into the third aperture 547C of the knotpusher 547, e.g., by using a wire threader, as shown in FIGS. 16AI-16AK.The slack or length of suture portions helps keep the knot portion 537Aaway from the distal tip of the LS delivery device 546 to inhibit and/orprevent the knot portion 537A from falling off (or being displaceddistally off of) the knot holder 541 during the threading process. Withthe free ends of the suture portions 532, 534 threaded proximallythrough the third aperture 547C in this manner, the LS delivery device546 is ready to be inserted into the target region (e.g., through anintroducer at an apical region of a heart) to deliver and deploy thelocking suture 537. Note that the alignment loop, slot, or guide 533Ccan be a loop configured to completely circumferentially surround thetether portions 532, 534, as shown in FIGS. 15D and 16AJ, or in otherinstances, the alignment loop, slot, or guide 533C can be a groove asshown, for example, in FIGS. 15E, 15F, and 15I.

As described in previous embodiments, the knot portion 537A can bedisplaced distally from the knot holder 541, and the knot portion 537can be slid or delivered along or about the suture portions 532, 534 toa suitable location within the target region, and then the LS deliverydevice 546 can be actuated to deploy the locking suture 537 such thatthe knot portion 537A secures, locks, or otherwise inhibits relativemovement between the portions of the suture portions 532, 534 physicallyengaged with the knot portion 537A. The deployed knot portion 537A isillustrated in FIG. 16AL. As shown, the suture portions 532, 534extending from the implants 531, 531′ are secured within the knotportion 537A of the suture lock 537, and the free ends of the sutureportion 532, 534, and the free ends of the locking suture 537 (e.g., thetether portion 537B) extend proximally from the knot portion 537B. Thefree ends of the suture portions 532, 534 and the tether portion 537B ofthe locking suture 537 can then be suitably tensioned and secured in asuitable location (e.g., via a proximal anchor outside of the targetregion, as described in connection with previous embodiments).

Either during deployment of the knot portion 537A and/or afterdeployment and when anchoring and tensioning the tether portion 537B ofthe locking suture 537, pulling proximally or tensioning the second freeend of the tether portion 537B will cause the knot portion 537A toradially compress or constrict, and pulling proximally or tensioning thefirst free end of the tether portion 537B will cause the proximal endand the distal end of the knot portion 537A to approximate, e.g.,laterally and/or angularly relatively deflect, as described, forexample, with respect to the knot portion 537A. As such, duringtensioning of the tether portion 537B, it is preferable to pull ortension the second free end of the tether portion 537B before pulling ortensioning the first free end of the tether portion 537B to limit orprevent loose loops or coils in the knot portion 537A when approximatingthe proximal and distal ends of the knot portion 537A.

In instances in which the implants 531, 531′ are secured within a heartand to heart valve leaflets, for example, deploying and anchoring thelocking suture 537 in the manner described above can put the valveleaflets in a desirable edge-to-edge relationship. Further, in additionto or instead of creating the edge-to-edge relationship, to promote alarger surface of coaptation, the implants 531, 531′ can be securedtogether to pull or otherwise move the posterior annulus towards theanterior leaflet and/or the anterior annulus towards to posteriorleaflet, thereby reducing the distance between the anterior annulus andthe posterior annulus, e.g., the septal-lateral distance by about10%-40%. Approximating the anterior annulus and the posterior annulus inthis manner can decrease the valve orifice, and thereby decrease, limit,or otherwise prevent undesirable regurgitation.

In some implementations, the tether portion 537B and/or the free ends ofthe suture portions 532, 534 can be selectively tensioned (e.g., pulledproximally while monitoring the valve leaflets and any associatedregurgitation). After confirming the desirable tension and heartfunction (e.g., reduced or a suitable amount of regurgitation), thetether portion 537B and the suture portions 532, 534 can be anchored(e.g., outside the apex of the ventricle) using knots, a pledget, a pad,or any other suitable anchoring mechanism.

FIGS. 17A-17W illustrate an alternate method of forming the lockingsuture described with reference to FIGS. 16A-16AK. Beginning after thestep illustrated in FIG. 16J (which corresponds to the step illustratedin FIG. 17A), the threader 570 is threaded under loops 5 and 6, asillustrated in FIG. 17B. The second free end is looped through thethreader 570 which pulls the second free end under loops 5 and 6,forming a loop, as illustrated in FIGS. 17C and 17D. The threader 570 isthen inserted through the newly formed loop of the second free end andunder loop 6, as illustrated in FIG. 17E. The first free end is thenlooped around and fed through the threader 570 and pulled under loop 6and through the loop formed by the second free end and tightened, asillustrated in FIGS. 17F-17H. The threader 570 is then placed throughthe newly formed loop of the first free end and under loop 6, asillustrated in FIG. 17I. The second free end is inserted through thethreader which pulls it under loop 6 and through the loop formed by thefirst free end, as illustrated in FIGS. 17J and 17K. The threader 570 isused to pull the first free end and the second free end throughrespective apertures of the pusher tube 547, as illustrated in FIGS.17L-17Q. The threader is then used to pull the first and second freeends through the central aperture of the pusher tube 547, as illustratedin FIGS. 17R and 17S.

FIG. 17T illustrates a single threader 570 being threaded through thepre-formed locking suture by going under loop 6, over loop 5, under loop4, over loop 3 and under loops 2 and 1. In this configuration, thelocking suture 537 and the LS delivery device 546 are ready to receivesuture ends 532, 534. The suture ends 532, 534 are fed through the endof the threader in FIG. 17U and pulled through the locking suture inFIGS. 17V and 17W, thereby threading the suture ends 532, 534 throughthe locking suture.

In the configuration illustrated in FIG. 17W, the locking suture isready to be delivered to a targeted location. Once at the targetlocation, the target suture can be deployed by applying forces on thefirst and second free ends, forming the knot tethers 537B.

An advantageous aspect of the LS delivery device 546, and other deliverydevices described herein, is the configuration of the apertures 547A,547B of the pusher tube 547. The placement of these apertures causes atargeted or tailored force vector when tightening the locking suture.Rather than applying a purely proximal longitudinal force, the apertures547A, 547B cause the suture free ends to pull radially out as well aslongitudinally. This advantageously causes the locking suture to tightenon the free suture ends while preventing or limiting proximal or distalmovement of the locking suture during the tightening procedure.

A benefit of the method of forming the locking suture illustrated inFIGS. 17A-17W is that it provides a way to use a single threader tointerweave suture tails through the pre-formed deployable lockingsuture. Thus, this method may be easier and less complicated toimplement than the method illustrated in FIGS. 16K-16AK.

FIGS. 18A-18K illustrate another example LS delivery device 1046 with atensioning mechanism that includes a rack and pinion configuration. TheLS delivery device includes a proximal portion 1036, a medial portion1038, and a distal portion 1040. The proximal portion 1036 forms ahandle 1035 to allow easy operation by a user. The proximal portion 1036also includes a rack 1042 that operably couples to a pinion gear 1044and a spring block 1048. The proximal portion 1036 also includes springplungers 1045 that are in contact with the spring block 1048, applying adownward force on the spring block 1048 causing it to apply a downwardforce on the rack 1042. A lever 1043 is coupled to the pinion gear 1044so that rotation of the lever 1043 causes the pinion gear 1044 to rotatewhich in turn causes the rack 1042 to move backward or forward along alongitudinal axis of the LS delivery device 1046.

The LS delivery device 1046 includes a pre-formed knot holder 1041 (anelongate member) coupled to the housing at the medial portion 1038 ofthe LS delivery device 1046. Similar to the other delivery devicesdisclosed herein, the knot holder 1041 is configured to secure apre-formed locking suture for delivery and to aid in transitioning thelocking suture from a delivery configuration to a deployedconfiguration. FIGS. 18A and 18C illustrate the LS delivery device in adelivery or pre-deployment configuration and FIGS. 18B and 18Dillustrate the LS delivery device in a deployed or post-deploymentconfiguration. As can be seen in the illustrations, to transition from apre-deployment configuration to a post-deployment configuration, thelever 1043 is rotated from the front to the back, or from pointingdistally to pointing proximally. FIGS. 18A and 18B illustrate the LSdelivery device 1846 with a portion of the housing removed to reveal theinteractions between the lever 1043, the pinion gear 1044, the rack1042, the spring block 1048, and the spring plungers 1045, while FIGS.18C and 18D illustrate the same configurations but the complete,enclosed housing.

In some embodiments, the spring block 1048 and the spring plungers 1045cooperate to limit the amount of tension applied by the rack 1042 on atether of a locking suture. When a sufficient tension is reached on thelocking suture tethers, the rack 1042 experiences an upward force causedby the interaction of the rack 1042 with the pinion gear 1044. Once thisforce surpasses a threshold, the spring block 1048 moves up so that theteeth of the rack 1042 disengage from the teeth of the pinion gear 1044.This can advantageously reduce the likelihood of over-tensioning thelocking suture which may cause the sutures to fray or otherwise becomedamaged.

FIG. 18E illustrates that a slotted needle knot holder 1075 can beinserted through the knot holder 1041. The slotted needle 1075 can beconfigured to allow a locking suture to be formed thereon.

FIGS. 18F and 18G illustrate a deployable locking suture 1037 formed onthe needle knot holder with a threader 1070 interweaved through thepre-formed locking suture, ready to receive suture ends. The ends 1037Bof the locking suture 1037 are fed through the knot holder 1041 and tiedor otherwise secured to a proximal end of the rack 1042, as illustratedin FIG. 18G.

FIG. 18H illustrates the slotted needle 1075 being withdrawn after thethreader 1070 has been used to interweave the sutures 1032, 1034 throughthe knot portion 1037A to leave the locking suture at the distal end ofthe knot holder 1041.

FIG. 18I illustrates the knot portion 1037A of the locking suture at thedistal end of the knot holder 1041 with the sutures 1032, 1034 threadedthrough the knot and the slotted needle 1075 being withdrawn. FIG. 18Jillustrates these same elements after the slotted needle 1075 has beencompletely withdrawn. Thus, the knot portion 1037A is positioned at thedistal end of the knot holder 1041 prior to deployment.

FIGS. 18K and 18L illustrate the knot portion 1037A after the lever 1043has been rotated to secure the knot 1037A. The rack 1042 is shown asprotruding proximally from the proximal portion of the LS deliverydevice 1046 to demonstrate pulling or tensioning of the locking suturetethers 1037B. As illustrated in FIG. 18M, the knot portion 1037A hasconstricted and tightened around the suture ends 1032, 1034 and can bereleased from the knot holder 1041.

FIG. 19 is a flow chart that illustrates a method 600 of delivering anddeploying a locking suture with a LS delivery device such as the LSdelivery device 546, for example, to approximate mitral valve leaflets,according to an embodiment. In some embodiments, the method includes, at600, threading a free end of a first suture extending from a firstimplant implanted on a distal side of a first mitral valve leaflet of aheart through a first coil of a locking suture when the locking sutureis disposed about a locking suture holder. The method further includes,at 602, threading a free end of a second suture extending from a secondimplant implanted on a distal side of a second mitral valve leaflet ofthe heart through a second coil of the locking suture when the lockingsuture is disposed about the locking suture holder. The method furtherincludes, at 604, introducing into a ventricle of the heart (1) thelocking suture disposed about the locking suture holder with the firstsuture threaded through the first coil and the second suture threadedthrough the second coil, and (2) a pusher having the locking sutureholder slidably disposed within a lumen defined by the pusher. Duringthe introducing, a distal end of the pusher is proximal to the firstcoil, the second coil, and a distal end of the locking suture holder.The method further includes, at 606, moving the pusher distally relativeto the locking suture holder to displace the first coil and the secondcoil off and distal to the distal end of the locking suture holder. Themethod further includes, at 608, withdrawing proximally the free end ofthe first suture and the free end of the second suture to cause thefirst coil and the second coil to compress to inhibit relative movementbetween the first coil, the second coil, and portions of the firstsuture and the second suture that are threaded through the first andsecond coils.

While in various embodiments described herein, methods have includedforming the knot portion of the locking suture with three cow hitches,in other embodiments any suitable number of cow hitches and/or othersuitable types of knot(s) could be used so long as the locking suturewhen deployed sufficiently secures the sutures disposed therein. In someembodiments, for example, a knot portion could be formed with less thanthree cow hitches (e.g., 1 or 2 cow hitches). In such embodiments,however, the gripping or securing force of the knot portion whendeployed may be less than that of a knot portion formed with three cowhitches, as described above. Without sufficient gripping or securingforce, the deployed locking suture may undesirably move or slip whenunder tension. In other embodiments, for example, more than three cowhitches could be used to form the knot portion. In such embodiments,however, additional cow hitches may increase the complexity and timerequired in forming the knot portion. Each additional cow hitch willrequire additional threading through the additional coils and mayintroduce additional slack or loose winds, thereby potentially reducingthe effectiveness of the locking suture once deployed.

While in various embodiments described herein, methods have includeddelivering distally a knot portion of a locking suture in a deliveryconfiguration to a suitable location within a target region, it shouldbe understood that for any of these embodiments, the process of delivery(prior to deployment) is adjustable (including reversible) in real-time.In this manner, if an operator pushes or delivers the knot portion toofar (e.g., identified as such under remote imaging or visualization),the operator can simply withdraw or retract proximally the LS deliverydevice or a suitable component thereof to withdraw or move proximallythe knot portion to place the knot portion in a suitable location, andthen deploy the knot portion as appropriate.

In alternative embodiments, instead of or in addition to using cowhitches, a locking suture can be in the form of one or more multi-turncoils of a suture that can be changed from an elongated configuration toa knot configuration by approximating opposite ends of the coil(s)towards each other, to form one or more loops, similar to or the same asany of the pre-formed knots or anchors described in U.S. Pat. No.8,852,213 (the '213 patent) and/or in International Application No. WO2017/059426, the disclosures of each of which are incorporated byreference herein in their entireties. Such a locking suture 737, forexample, is shown in an elongated configuration in FIG. 20 and in adeployed, bulky knot configuration, in FIG. 21. As shown in FIG. 20, thelocking suture 737 is disposed about a knot holder 741 that is slidablydisposed within a lumen of a knot pusher 747. With the locking suture737 disposed in its elongated configuration about the knot holder 741,the free ends of the suture portions 732, 733, 734, 735 (e.g., extendingfrom implants implanted within a heart of a patient; not shown), arerouted through the coils of the locking suture 737 from its distal endto a medial portion (e.g., through the portion separating the two loopsformed during deployment, as described below and shown in FIG. 21). Inthis manner, the locking suture 737 can be deployed to change from itselongated configuration to its knot configuration, as shown in FIG. 21,by approximating opposite ends of the coils towards each other, to formtwo loops. For example, as described in connection with the distalanchor 140 of the '213 patent, the strands or lengths of the sutures canextend from opposite ends of the elongate coiled portion and extendthrough a delivery device, and then the proximal ends of the suture canbe pulled proximally to cause opposite ends of the coiled portions to bepulled towards each other to form the loops. With the locking suture 737deployed, the suture portions 732-736 can be secured to inhibit relativemovement therebetween as described in connection with previousembodiments.

Although in this embodiment the suture portions are threaded through thedistal end of the locking suture and out the medial portion, in otherembodiments, the suture portions can be threaded in any suitable manner.For example, one or more (including all) of the suture portions can bethreaded through the distal end to the proximal end of the coils,through the proximal end to the distal end of the coils, through theproximal end and out the medial portion of the coils, through the medialportion of the coils and to the distal or proximal end, and/orinterlaced (e.g., in and out of) throughout the coils. In suchembodiments, each free end or length of suture portion can be routedtogether or separately and through varying pathways. In yet furtheralternative embodiments, a single set of coils could be used and thesuture tails or free ends can be interlaced with the locking suture inany suitable manner.

Repairing a cardiac valve (e.g., a mitral valve) by implanting a distalanchor or implant, as described herein, is often influenced by apatient's particular anatomy. When the combined length of the posteriorleaflet and the anterior leaflet is significantly larger than the A-Pdimension of the mitral valve, the likelihood of a successful repair issignificantly higher. For example, a patient having a large posteriorleaflet is desirable, as a large posterior leaflet provides a largesurface of coaptation with the anterior leaflet, thereby providing asufficient seal when the leaflets coapt, e.g., to limit regurgitation.Conversely, a patient having a small posterior leaflet will have arelatively smaller surface of coaptation. Similarly, a patient having alarge anterior leaflet can help lead to a desirable and successfulrepair. Ultimately, the effectiveness and durability of a repair of thisnature is influenced greatly by the amount of anterior and posteriorleaflet tissue coapting together during systole. As another example,some patients have a relatively large valve orifice (e.g., the orificemay dilate over time due to illness), and as a result are prone to lessleaflet coaptation and increased regurgitation. Ensuring sufficientcoaptation is addressed by various embodiments described herein,including the following examples.

FIGS. 22A-22C illustrate an edge-to-edge procedure for a mitral valve1122 using the locking sutures and delivery devices described herein.The mitral valve 1122 includes two leaflets, the anterior leaflet 1152and the posterior leaflet 1154, and a diaphanous incomplete ring aroundthe valve, called the annulus 1153. FIG. 22A illustrates the ventricularside of the mitral valve 1122. A delivery device 1146 delivers a lockingsuture to a targeted location along sutures 1132, 1134. FIG. 22Billustrates edge-to-edge approximation of the mitral valve leaflets1152, 1154 with the locking suture 1137A placed at or near the tissue.FIG. 22C illustrates the atrial side of the mitral valve 1122, withdistal anchors 1131, 1131′ visible.

While various embodiments described above include deploying a lockingsuture to sutures extending from implants deployed near the free edge ofmitral valve leaflets to perform an edge-to-edge or Alfieri procedure,in some implementations, the implants can be alternatively oradditionally deployed in other locations to facilitate other types ofcardiac repairs necessitated by various cardiac issues (e.g., smallposterior leaflet, large orifice, leaflet clefts, etc.), some of whichare described below.

In some embodiments, for example, the implants can be placed near thefree edge of the anterior and posterior leaflets, and the cordsextending therefrom can be approximated and secured together using themethods and devices described above to improve coaptation of theanterior and posterior leaflets. For example, in a patient who has arelatively large valve orifice (e.g., due to dilation of the orificeover time due to illness), and as a result is prone to less leafletcoaptation and increased regurgitation, approximating the implants canincrease available leaflet surfaces for coaptation. Additionally, thesecured sutures (and/or the tether portion of the locking suture) can besuitably tensioned and/or pulled towards the access site and into theventricle of the heart, resulting in a larger surface area ofcoaptation, and improved coaptation between the leaflets.

Further, to promote a larger surface of coaptation, in some embodiments,implants can be deployed in the body of the leaflets and/or at or nearthe annulus of the anterior and posterior leaflets, and the cordsextending therefrom can be secured together and pulled to move theposterior annulus towards the anterior leaflet and/or the anteriorannulus towards the posterior leaflet, thereby reducing the distancebetween the anterior annulus and the posterior annulus, e.g., theseptal-lateral distance, by about 10%-40%. Said another way,approximating the anterior annulus and the poster annulus in this mannercan decrease the valve orifice, and thereby decrease, limit, orotherwise prevent undesirable regurgitation.

While various embodiments described herein have included two implantsand two sets of cords, and one locking suture, in variousimplementations, any suitable number of implants and any suitable numberof sets of cords and any suitable number of locking sutures can bedelivered and deployed to approximate various portions of the heart tocombat the cardiac issues described herein. For example, in someembodiments, three or more sets of cords can be approximated and securedtogether using one or more locking sutures to approximate two, three ormore implants. In some instances, for example, the heart can beeffectively re-shaped (e.g., improve orifice geometry, improve relativeleaflet geometry, etc.) by strategically deploying multiple implants andsecuring multiple cords extending therefrom using the methods anddevices described herein.

As another example, in some instances, it may be desirable to decrease agap between a valve commissure (e.g., the edge of the valve where theleaflets come together). In such instances, a first implant can bedeployed on the posterior leaflet near the commissure and a secondimplant can be deployed on the anterior leaflet near the commissure.With both the first implant and second implant deployed in this manner,the cords extending therefrom can be interlaced to approximate the firstimplant and the second implant such that the gap between the commissureis limited, decreased, or eliminated.

As another example, in some instances in which a patient has a cleftedleaflet, two or more implants can be deployed on either side of thecleft. The cords extending therefrom can then be approximated andsecured together to approximate the implants such that the cleft in theleaflet is limited, decreased, or eliminated.

As another example, the valve annulus and/or orifice can be optimizedand/or reduced in size by deploying multiple anchors and cords extendingtherefrom in various locations within the heart to effectively deliverthe equivalent of an additional papillary muscle or a prostheticpapillary muscle (PPM). For example, in some instances, six implants canbe deployed to a mitral valve, and all the cords extending from the siximplants can be approximated and secured together using a locking sutureto effectively create a single anchor common to all of the cords.Deploying multiple implants and securing or approximating the cords inthis manner can provide the functionality otherwise provided by aproperly functioning papillary muscle.

The above-described procedures can be performed manually, e.g., by aphysician, or can alternatively be performed fully or in part withrobotic or machine assistance. For example, in some embodiments, a LSdelivery device can be configured to deliver and deploy a locking sutureautomatically. Further, although not specifically described for someembodiments, in various embodiments, the heart may receive rapid pacingto minimize the relative motion of the edges of the valve leafletsduring the procedures described herein (e.g., while the sutures andlocking suture is being delivered and deployed).

Additional Embodiments and Terminology

While various embodiments have been described above, it should beunderstood that they have been presented by way of example only, and notlimitation. Where methods described above indicate certain eventsoccurring in certain order, the ordering of certain events may bemodified. Additionally, certain of the events may be performedconcurrently in a parallel process when possible, as well as performedsequentially as described above.

Where schematics and/or embodiments described above indicate certaincomponents arranged in certain orientations or positions, thearrangement of components may be modified. While the embodiments havebeen particularly shown and described, it will be understood thatvarious changes in form and details may be made. Any portion of theapparatus and/or methods described herein may be combined in anycombination, except mutually exclusive combinations. The embodimentsdescribed herein can include various combinations and/orsub-combinations of the functions, components and/or features of thedifferent embodiments described.

The present disclosure describes various features, no single one ofwhich is solely responsible for the benefits described herein. It willbe understood that various features described herein may be combined,modified, or omitted, as would be apparent to one of ordinary skill.Other combinations and sub-combinations than those specificallydescribed herein will be apparent to one of ordinary skill, and areintended to form a part of this disclosure. Various methods aredescribed herein in connection with various flowchart steps and/orphases. It will be understood that in many cases, certain steps and/orphases may be combined together such that multiple steps and/or phasesshown in the flowcharts can be performed as a single step and/or phase.Also, certain steps and/or phases can be broken into additionalsub-components to be performed separately. In some instances, the orderof the steps and/or phases can be rearranged and certain steps and/orphases may be omitted entirely. Also, the methods described herein areto be understood to be open-ended, such that additional steps and/orphases to those shown and described herein can also be performed.

Unless the context clearly requires otherwise, throughout thedescription and the claims, the words “comprise,” “comprising,” and thelike are to be construed in an inclusive sense, as opposed to anexclusive or exhaustive sense; that is to say, in the sense of“including, but not limited to.” The word “coupled”, as generally usedherein, refers to two or more elements that may be either directlyconnected, or connected by way of one or more intermediate elements.Additionally, the words “herein,” “above,” “below,” and words of similarimport, when used in this application, shall refer to this applicationas a whole and not to any particular portions of this application. Wherethe context permits, words in the above Detailed Description using thesingular or plural number may also include the plural or singular numberrespectively. The word “or” in reference to a list of two or more items,that word covers all of the following interpretations of the word: anyof the items in the list, all of the items in the list, and anycombination of the items in the list.

The disclosure is not intended to be limited to the implementationsshown herein. Various modifications to the implementations described inthis disclosure may be readily apparent to those skilled in the art, andthe generic principles defined herein may be applied to otherimplementations without departing from the spirit or scope of thisdisclosure. The teachings of the invention provided herein can beapplied to other methods and systems, and are not limited to the methodsand systems described above, and elements and acts of the variousembodiments described above can be combined to provide furtherembodiments. Accordingly, the novel methods and systems described hereinmay be embodied in a variety of other forms; furthermore, variousomissions, substitutions and changes in the form of the methods andsystems described herein may be made without departing from the spiritof the disclosure. The accompanying claims and their equivalents areintended to cover such forms or modifications as would fall within thescope and spirit of the disclosure.

What is claimed is:
 1. A method for using locking sutures to approximateanchor implants attached to targeted tissue, the method comprising:attaching two or more cords to targeted tissue, individual cordsincluding a distal anchor implant and a suture extending proximally fromthe distal anchor implant; intertwining proximal end portions of the twoor more sutures with a locking suture, the locking suture including aknot portion and a tether portion extending from the knot portion andconfigured to be manipulated to transition the knot portion from adelivery configuration to a deployed configuration; positioning the knotportion of the locking suture along the two or more sutures toapproximate portions of the targeted tissue; transitioning the knotportion from the delivery configuration to the deployed configuration tolock the locking suture; and receiving feedback from a visualizationsystem, the feedback including an approximation of the targeted tissue.2. The method of claim 1, wherein transitioning the knot portion to thedeployed configuration does not increase proximal forces on the targetedtissue.
 3. The method of claim 1, wherein the targeted tissue is withina targeted region and positioning the knot portion is done utilizing alocking suture device that is operated outside of the targeted region.4. The method of claim 3, wherein the targeted region is the heart. 5.The method of claim 4 further comprising anchoring the proximal endportions of the two or more sutures.
 6. The method of claim 5, whereinanchoring the proximal end portions includes securing the proximal endportions to an external wall of the heart.
 7. The method of claim 1,wherein the targeted tissue includes a leaflet of a mitral valve.
 8. Themethod of claim 1 further comprising securing the knot portion to adistal end of a locking suture delivery device.
 9. The method of claim8, wherein transitioning the knot portion to the deployed configurationincludes manipulating an element of the locking suture delivery deviceto which the locking suture is secured.
 10. The method of claim 8further comprising applying sequential proximal forces to the proximalend portions using the locking suture delivery device.
 11. The method ofclaim 1, wherein positioning the locking suture along the sutures of thetwo or more sutures results in a point of intersection that approachesthe targeted tissue to change a force vector on the two or more cordsattached to the targeted tissue.
 12. A locking suture delivery anddeployment device comprising: a body having a tip portion at a distalend, the tip portion being configured to be atraumatic to targetedtissue; a holding component coupled to the body, the holding componenthaving one or more features to secure a pre-formed knot of a lockingsuture at the distal end, the locking suture including a tether portionwith two proximal ends; a release component in communication with theholding component, the release component configured to release thepre-formed knot after it has been transitioned from a deliveryconfiguration to a deployed configuration; and a tensioning componentcoupled to the body, the tensioning component configured to applyproximal forces to individual proximal ends of the tether portion atdifferent times with targeted tension.
 13. The device of claim 12,wherein the tensioning component is configured to transition thepre-formed knot from the delivery configuration to the deployedconfiguration without increasing tension on the targeted tissue.
 14. Thedevice of claim 12, wherein the tensioning component includes a rack andpinion configuration.
 15. The device of claim 12, wherein the releasecomponent includes a pusher member to push the pre-formed knot from theholding component.
 16. The device of claim 12, wherein the tensioningcomponent is configured to apply a first force to a first proximal endportion of the tether portion and to apply a second force to a secondproximal end of the tether portion.
 17. The device of claim 16, whereinthe tensioning component is configured to apply the first force and thesecond force sequentially without human intervention between applicationof the first force and the second force.
 18. The device of claim 16,wherein the first force and the second force are different from oneanother.
 19. The device of claim 12, wherein the tensioning component isconfigured to automatically stop increasing tension at a targetedtension.
 20. The device of claim 12, wherein the tensioning componentincludes a feedback mechanism to indicate when a targeted tension isachieved.